Laboratory of Tumor Immunology and Biology

Chief
Jeffrey Schlom, Ph.D.

Mission

The Laboratory of Tumor Immunology and Biology (LTIB) functions as a multidisciplinary and interdisciplinary translational research programmatic effort with the goal of developing novel immunotherapies for cancer. The LTIB strategic plan focuses on the development of novel immunotherapeutics, not only as monotherapies, but more importantly, in combination with other immune-mediating modalities, and other conventional or experimental therapies, as part of an immuno-oncology programmatic effort. Within this effort are several research groups and a clinical trials group, and multiple collaborations with intramural and extramural scientific and clinical investigators, and with investigators in the private sector.

Organization

Office of the Chief:  Dr. Jeffrey Schlom (Senior Investigator, Laboratory Chief). This office is responsible for the administrative functions of the LTIB, such as travel, personnel actions, training, meetings, manuscript editing, purchasing, etc.

Immunoregulation Group:  Dr. Claudia Palena (Senior Investigator, Section Head). This group investigates mechanisms of tumor progression, including mechanisms of metastasis and tumor resistance to therapies, and how immune-based therapies can be employed as therapeutics directed against such tumor-cell phenotypes. These studies have led to the identification and analyses of transcription factors that are drivers of the phenomenon of epithelial-to-mesenchymal transition (EMT) and to ongoing clinical studies employing vaccines directed against one of these gene products.

Recombinant Vaccine Group:  Dr. James Hodge (Senior Investigator, Section Head). This group investigates how non-immune-based therapies affect tumor cells and specific components of the immune system. An emphasis is placed on the mechanisms of how standard-of-care and new experimental therapies alter tumor cells to render them more susceptible to immune-based therapies. These studies form the rationale for novel immune- and non-immune-based combination clinical trials.

Immunomodulation Group: Dr. Sofia Gameiro (Staff Scientist, Group Head). This group examines how emerging therapeutics can modulate the immune system to exert potent antitumor activity, with particular emphasis on how the mechanisms involved can be exploited to maximize antitumor activity in combination regimens with novel immunotherapies and other anticancer modalities. These studies form the rationale for novel hypothesis-driven clinical interventions.

Cytokine Group:  Dr. John Greiner (Staff Scientist, Group Head). This group investigates the mechanisms by which cytokines and other immune modulators affect the host immune system and the tumor microenvironment for use in combination with immunotherapeutics and other forms of cancer therapy.

Cellular Immunology Group:  Dr. Caroline Jochems Frohlich (Staff Scientist, Group Head). This group is involved in studies to identify and modify tumor-associated antigens to enhance their immunogenicity in cancer patients in vaccine-mediated immunotherapy. The group also studies patients' immune responses to provide critical information toward the development of more effective immunotherapeutic approaches to cancer.

Molecular Immunology Group:  Dr. Renee Donahue (Staff Scientist, Group Head). In this group emphasis is placed on the identification of specific immune cell subsets that can help identify cancer patients most likely to benefit from immunotherapy. This group also studies the tumor microenvironment and specific immune cell subsets in the periphery, pre- and post-immunotherapy, to identify potential correlations with clinical responses of patients treated with immunotherapies as monotherapy or combination therapy.

Immunotherapeutics Group:  Dr. Duane Hamilton (Staff Scientist, Group Head). This group focuses on the identification and characterization of tumor-specific antigens and neoepitopes. This group evaluates techniques to identify tumor antigens unique to a patient’s own tumor. It is this group's belief that vaccinating patients with neoepitopes uniquely expressed by their tumor will improve the breadth of anti-tumor immunity generated by the lab's vaccine platforms, and result in greater immunological control of tumor growth.

Clinical Trials Group: Dr. Julius Strauss (Assistant Research Physician, Group Director). This group designs and conducts science-driven clinical studies as a consequence of hypothesis-driven preclinical studies in the laboratory. Dr. Strauss works closely with the following oncologists who also have joint appointments in the LTIB: Drs. James Gulley, Ravi MadanJason RedmanMarijo Bilusic and Fatima Karzai (Genitourinary Malignancies Branch); with Dr. Margaret Gatti-Mays (Division of Medical Ocology, The James Cancer Hospital and The Ohio State Comprehensive Cancer Center), a Special Volunteer at the NIH; and with Dr. Schlom and other LTIB staff members as a well-integrated immunotherapy team. This group also serves as the conduit for collaborative trials with clinical investigators in other NCI Branches and at numerous extramural Cancer Centers.

STRATEGIC PLAN

The LTIB program takes advantage of the uniqueness of the NCI intramural program in that it spans high-risk basic discovery research in immunology and tumor biology, through preclinical translational research, to paradigm-shifting clinical trials. Focus is placed on the design and development of novel 'off-the-shelf' recombinant immunotherapeutics and immunomodulators that can be used in clinical studies at numerous institutions, and do not involve costly and labor-intensive ex vivo manipulations that can be carried out in only one or two centers. This is accomplished in part via Cooperative Research and Development Agreements (CRADAs) with partners in the private sector. The immunotherapeutics and immune modulators that we have developed have also enabled multiple collaborations with clinical investigators at extramural Cancer Centers.

While the use of checkpoint inhibitor monoclonal antibodies (MAb) has shown clear clinical benefit in patients with melanoma, and some other malignancies, in the vast majority of solid tumors <20% of patients benefit from this class of therapies. The LTIB has been and is involved in the design and development of a spectrum of immunotherapeutic and immunomodulatory agents. Preclinical studies have been completed or are ongoing with a range of agents, and clinical studies using many of these agents as monotherapies or in combination therapies are either completed, ongoing or planned to begin shortly.

The preclinical and clinical immunotherapy studies employing a spectrum of different immunotherapeutic agents including vaccines, checkpoint inhibitors, immune modulators, and inhibitors of immune suppressive entities have the potential to convert tumors that currently do not respond to checkpoint inhibition monotherapy (so-called “cold tumors”) into permissive immunogenic targets leading to clinical benefit in patients with multiple types of tumors. A major emphasis of these studies is to also better understand the mechanisms of both host immune cell activation and resistance of tumors to immunotherapeutic approaches, both within the tumor microenvironment and in the peripheral immunome. It may also define which patients will respond to combination immunotherapies when interrogated either (a) prior to the initiation of treatment or (b) early in the therapeutic regimen. These studies may also define which patients will most likely develop autoimmune events when the peripheral immunome is interrogated either prior to the initiation of therapy or early in the therapeutic regimen.

Agents Under Preclinical and Clinical Investigation as Monotherapy or in Combination Therapies Are:

  • Recombinant vaccines: (a) Poxviral vectors expressing three costimulatory molecules and expressing transgenes for either PSA, CEA plus MUC1, or brachyury. The transcription factor brachyury has been identified as a driver of the epithelial-to-mesenchymal transition (EMT) process, stemness, and resistance to therapy. (b) Admixtures of proprietary recombinant adenovirus vectors containing transgenes for brachyury, CEA, MUC1, PSA, and tumor neoepitopes.
  • Checkpoint inhibitors: (a) anti-PDL1 (avelumab) and (b) anti-PDL1/TGF-betaR2 (TRAP).
  • Immune enhancers: (a) IL-15/Ra/Fc immunocytokine (Alt-803), (b) tumor targeting IL-12 immunocytokine (NHS-IL12), and (c) IDO inhibitor.
  • Costimulators: agonist antibodies to OX40, 41BB, and GITR.
  • Inhibitors of immune suppressive entities: (a) anti-IL8 MAb, (b) small molecule IL-8 inhibitor (IL-8 receptor antagonist), and (c) anti-PDL1/TGF-betaR2 (TRAP).

 

Clinical Trials Ongoing, Recently Completed or In Review Involving LTIB Activities:

The major goals of these studies are (a) to conduct science-driven clinical studies of specific immunotherapeutics based on hypothesis-generated preclinical experimentation, and (b) to conduct "proof of concept" clinical studies employing specific immunotherapeutics as part of an immuno-oncology platform. There are four major components to LTIB clinical trials: (a) preclinical studies providing the rationale, (b) preparation of INDs and protocols, etc., and appropriate reviews, (c) the clinical trials, and (d) analyses of patients' immune responses and clinical correlates. Collaborative clinical studies are also ongoing with clinical investigators in the LTIB and in several other Branches of the Center for Cancer Research, NCI, and with clinicians at several extramural Cancer Centers.

Ongoing intramural clinical trials:

  • Phase I/II trial of combination immunotherapy in subjects with advanced HPV associated malignancies (PDS0101+M7824+M9241) (PI, Strauss)
  • Phase II trial of M7824 in subjects with HPV positive malignancies (PI, Strauss)
  • First-in-human Phase I trial of NHS-IL12 in subjects with metastatic solid tumors (PI, Gulley)
  • A Phase I, open-label, multiple-ascending dose trial to investigate the safety, tolerability, pharmacokinetics, biological and clinical activity of avelumab (MSB0010718C), a monoclonal anti-PD-L1 antibody, in subjects with metastatic or locally advanced solid tumors and expansion to selected indications (PI, Gulley)
  • A Phase Ib open label, dose finding trial to evaluate the safety, tolerability, and pharmacokinetics of avelumab in combination with M9241 (NHS-IL12) in subjects with locally advanced, unresectable, or metastatic solid tumors (PI, Gulley)
  • A Phase I/II study of immunotherapy combination BN-brachyury vaccine, M7824, ALT-803 and Epacadostat (QuEST1) (PI, Gulley)
  • Phase I Study of PROSTVAC in combination with nivolumab in men with prostate cancer (PI, Gulley)
  • Phase II trial of combination immunotherapy (Prostvac, CV301 and M7824) in biochemically recurrent prostate cancer (PI, Madan)
  • Phase I open label trial of intravenous administration of MVA-BN-brachyury vaccine in patients with advanced cancer (PI, Bilusic)
  • A pilot study to investigate the safety and clinical activity of avelumab (MSB0010718C) in thymoma and thymic carcinoma after progression on platinum-based chemotherapy (PI, Rajan)
  • Phase IB/II single-arm study of M7824 in with gemcitabine in adults with previously treated advanced adenocarcinoma of the pancreas (PI, Rudloff)
  • Phase II trial of a combination of ATR inhibitor M-6220 and low-dose topotecan with M7824, a novel bifunctional fusion protein targeting PD-L1 and TGF-β pathways in small cell cancers (PI, Thomas/Pommier)
  • A Phase I study of interleukin-15 in combination with avelumab (Bavencio) in relapsed/refractory mature t-cell malignancies (PI, Miljkovic)
  • A phase II pilot study of avelumab in combination with hypofractionated radiotherapy in patients with relapsed refractory multiple myeloma (PI, Kazandijan)
  • Phase II trial of avelumab (Bavencio®) with IL-15 in subjects with clear-cell renal carcinoma (PI, Waldmann/Conlan)

Ongoing extramural clinical trials:

  • A phase II trial of avelumab a fully humanized antibody that target cells expressing PDL1 in patients with recurrent or progressive osteosarcoma (St Jude’s, PI, Bishop)
  • A phase II trial of perioperative CV301 Vaccination in Combination with Nivolumab and Systemic Chemotherapy for Resectable Hepatic-limited metastatic colorectal cancer (Rutgers, PI, Carpizo)
  • A phase I/II trial of the PD-L1 inhibitor, durvalumab (MEDI4736) plus CV301 in combination with maintenance chemotherapy for patients with metastatic colorectal or pancreatic adenocarcinoma (Georgetown University, PI, Pishvaian/Weinberg)
  • OXEL: A pilot study of immune checkpoint or capecitabine or combination therapy as adjuvant therapy for triple negative breast cancer with residual disease following neoadjuvant chemotherapy (Georgetown University, PI, Lynce)
  • A pilot trial of induction talazoparib followed by combination of talazoparib and avelumab in advanced breast cancer: the TALAVE study (Georgetown University, PI, Lynce)
  • Phase II randomized, placebo-controlled trial of PROSTVAC (PSA-TRICOM) in patients with clinically localized prostate cancer undergoing active surveillance (University of Arizona, PI, Chow)

Completed clinical trials:

  • A randomized Phase II trial of standard of care alone or in combination with Ad-CEA vaccine and avelumab in patients with previously untreated metastatic colorectal cancer (PI, Strauss)
  • CV301 Single Patient Study (PI, Gatti-Mays)
  • A Phase I, open-label, multiple-ascending dose trial to investigate the safety, tolerability, pharmaco-kinetics, biological and clinical activity of MSB0011359C (M7824) in subjects with metastatic or locally advanced solid tumors with expansion to selected indications (PI, Gulley)
  • A randomized phase II trial combining vaccine therapy with PROSTVAC /TRICOM and enzalutamide vs. enzalutamide alone in men with metastatic castration resistant prostate cancer (PI, Madan)
  • Docetaxel and PROSTVAC for metastatic castration sensitive prostate cancer (PI, Madan)
  • Open-label phase II trial to evaluate the safety and tolerability of MVA priming and fowlpox booster (MVA-BN-brachyury/FPV-brachyury) (PI, Bilusic)
  • Treatment of patients with castration resistant prostate cancer using multi-targeted recombinant Ad5 PSA/MUC1/brachyury based immunotherapy vaccines (PI, Bilusic)
  • A phase II study of M7824 in subjects with recurrent respiratory papillomatosis (PI, Hinrichs)
  • Phase I trial using a multi-targeted recombinant Ad5 (CEA/MUC1/Brachyury)–based immunotherapy vaccine regimen in patients with advanced cancer (PI, Strauss)
  • A CV301 phase 1/1b study followed by randomized phase 2 study of CV301 in combination with nivolumab versus nivolumab in subjects with previously treated non-small cell lung cancer (PI, Gulley)
  • A randomized, double-blind, Phase 2 trial of GI-6301 (yeast-brachyury vaccine) versus placebo in combination with standard of care definitive radiotherapy in locally advanced, unresectable, chordoma (PI, Gulley)
  • A phase II trial of enzalutamide in combination with PSA-TRICOM in patients with non-metastatic castration sensitive prostate cancer (PI, Madan)
  • Prostvac in patients with biochemical recurrent prostate cancer (PI, Madan)
  • A phase I study of avelumab in subjects with recurrent respiratory papillomatosis (PI, Hinrichs)
  • A phase II, open-label, multicenter trial to investigate the clinical activity and safety of MSB0010718C in subjects with merkel cell carcinoma (PI, Brownell)

Clinical trials in review:

  • BrEAsT: A phase Ib trial of sequential combinations of BN-brachyury, entinostat, ado-trastuzumab emtansine and M7824 in advanced stage breast cancer (PI, Gatti-Mays)
  • An open-label, Phase I dose-escalation study investigating the safety, tolerability, pharmacokinetics, biological and clinical activity of M6903 (anti-TIM3 antibody) in combination with M7824 in subjects with advanced solid tumors (PI, Redman)
  • A phase I study of TGF-β trap (M7824) and NHS-IL12 (M9241) alone and in combination with stereotactic body radiation therapy (SBRT) in adults with metastatic non-prostate genitourinary malignancies (PI, Apolo)
  • Retrospective study of M7824 related adverse effects in adults with cancer (PI, Brownell)
  • Phase I/II of NHS-IL12 monotherapy and in combination with M7824 in advanced Kaposi sarcoma (PI, Yarchoan)
  • QUICC: Phase II trial of combination immunotherapy in subjects with advanced small bowel and colorectal cancers (PI, Strauss)
  • WOOT: Phase I/II trial of HPV vaccine PRGN-2009 alone or in combination with anti-PD-L1/TGFß trap (M7824) in subjects with HPV positive cancers (PI, Strauss)
  • STAT: Phase I/II trial investigating the safety, tolerability, pharmacokinetics, immune and clinical activity of SX-682 in combination with Bintrafusp alfa (M7824 or TGF-b “trap”/PD-L1) with BN-CV301 TRICOM in advanced solid tumors (PI, Gatti-Mays)
  • ABC trial: abemaciclib + M7824 + CV301 +- N-803 in HR+ breast cancer (PI Gatti-Mays)
  • A phase I/II study of PD-L1 t-haNK cells plus Immunotherapy in Subjects with Advanced Cancer (PI, Redman)
  • A sequential window of opportunity trial of anti-PD-L1/TGF-β trap (M7824) alone and in combination with TriAd vaccine, and N-803 for p16-negative resectable head and neck squamous cell carcinoma (PI, Redman)
  • Chemoimmunotherapy of prostate cancer mCRPC and mCSPC (docetaxel + ADT + M7824 + M9241) (PI, Madan)
  • A phase 1/2, open-label, dose-escalation, safety and tolerability study of NC410 in subjects with advanced or metastatic solid tumors (PI, Bilusic)
  • BEST: phase I/II trial of the combination of Bintrafusp alfa (M7824), entinostat and NHS-IL12 (M9241) in patients with advanced cancer (PI, Sater)
  • Phase 2 study of Bintrafusp alpha in recurrent/metastatic olfactory neuroblastoma (BARON) (PI, Floudas)
  • A phase II, open-label trial of Bintrafusp alfa (M7824) in subjects with thymoma and thymic carcinoma (PI, Rajan)

 

Recent Selected Publications:

  • Strauss J … Schlom J, Gulley JL. Bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with human papillomavirus–associated malignancies. J Immunother Cancer (in press)
  • Smalley Rumfield C … Schlom J. Therapeutic vaccines for HPV-associated malignancies (review). ImmunoTargets Ther (in press).
  • Schlom J and Donahue RN. The importance of cellular immunity in the development of vaccines and therapeutics for COVID-19 (Perspective). J Infect Dis. 222(9):1435-1438, 2020.
  • Lee KL, Schlom J, Hamilton DH. Combination therapies utlizing neoepitope-targeted vaccines (review). Cancer Immunol Immunother (in press).
  • Morillon II YM … Schlom J. The development of next-generation PBMC humanized mice for preclinical investigation of cancer immunotherapeutic agents. Anticancer Res. 40: 5329-5341, 2020.
  • Robbins Y… Schlom J, Hodge JW, Allen CT. Tumor control targeting PD-L1 with chimeric antigen receptor modified NK cells. eLife. 9:e54854, 2020.
  • Del Rivero J … Schlom J, Gulley JL, Madan RA. A case report of sequential use of a yeast-CEA therapeutic cancer vaccine and anti-PD-L1 inhibitor in metastatic medullary thyroid cancer. Front Endocrinol. 11:490, 2020.
  • Fabian KP … Schlom J, Hodge. PD-L1-targeting high-affinity NK cells (PD-L1 t-haNK) induce direct antitumor effects and target suppressive MDSC populations. J Immunother Cancer 8(1):e000450, 2020.
  • Smalley Rumfield C … Schlom J. Immunomodulation to enhance the efficacy of an HPV therapeutic vaccine. J Immunother Cancer. 8(1):e000612, 2020.
  • Solocinski K … Schlom J, Hodge JW. Overcoming hypoxia-induced functional suppression of NK cells. J Immunother Cancer 8(1) e000246, 2020.
  • Morillon II YM … Schlom J. The use of a humanized NSG-β2m−/− model for investigation of immune and anti-tumor effects mediated by the bifunctional immunotherapeutic bintrafusp alfa. Front Oncol. 10:549, 2020.
  • Knudson KM ... Schlom J, Gameiro SR. Rationale for IL-15 superagonists in cancer immunotherapy. Exp Op Biol Ther. 11:1-5, 2020.
  • Knudson KM … Schlom J. Functional and mechanistic advantage of the use of a bifunctional anti-PD-L1/IL-15 superagonist. J Immunother Cancer 8(1):e00049, 2020.
  • Abdul Sater H … Schlom J … Gulley JL. Neoadjuvant PROSTVAC prior to radical prostatectomy enhances T-cell infiltration into the tumor immune microenvironment in men with prostate cancer. J Immunother Cancer 8(1):e000655, 2020.
  • Horn LA … Schlom J, Palena C. Simultaneous inhibition of CXCR1/2, TGF-β, and PD-L1 remodels the tumor and its microenvironment to drive anti-tumor immunity. J Immunother Cancer 8(1):e000326, 2020.
  • Lind H … Schlom J. Dual targeting of TGF-β and PD-L1 via a bifunctional anti-PD-L1/TGF-βRII agent: status of preclinical and clinical advances. [review] J Immunother Cancer 8(1):e000433, 2020.
  • Greene S … Schlom J … Allen C. Inhibition of myeloid cell trafficking with dual CXCR1 and CXCR2 blockade enhances NK cell immunotherapy. Clin Cancer Res. 26:1420-1431, 2020.
  • Collins JM … Schlom J, Gulley JL, Bilusic M. Phase I trial of a modified vaccinia Ankara (MVA) priming vaccine followed by a fowlpox virus (FPV) boosting vaccine modified to express brachyury and costimulatory molecules in advanced solid tumors. The Oncologist. 25(7):560-e1006, 2020.
  • Giles AJ … Schlom J … Park DM. Efficient ADCC-killing of meningioma by avelumab and a high-affinity natural killer cell line, haNK. JCI Insight. 4(20), 2019.
  • Hicks KC … Schlom J. Cooperative immune-mediated mechanisms of the HDAC inhibitor entinostat, an IL-15 superagonist, and a cancer vaccine effectively synergize as a novel cancer therapy. Clin Cancer Res. 26:704-716, 2020.
  • Rajan A … Schlom J … Gulley JL. Efficacy and tolerability of anti-programmed death-ligand 1 (PD-L1) antibody (avelumab) treatment in advanced thymoma. J ImmunoTher Cancer. 7(1):269, 2019.
  • Bilusic M … Schlom J, Gulley JL. Phase I trial of HuMax-IL8 (BMS-986253), an anti-IL-8 monoclonal antibody, in patients with metastatic or unresectable solid tumors. J Immunother Cancer 7(1):240, 2019.
  • Gatti-Mays ME … Schlom J … Strauss J. A phase I trial using a multi-targeted recombinant Ad5 (CEA/MUC1/Brachyury)–based immunotherapy vaccine regimen in patients with advanced cancer. The Oncologist [Clinical Trial Results Section]. 24:1-6, 2020.
  • Lee KL … Schlom J. Efficient tumor clearance and diversified immunity through neoepitope vaccines and combinatorial immunotherapy. Cancer Immunol Res. 7:1359-1370, 2019.
  • Morillon YM … Schlom J. Temporal changes within the (bladder) tumor microenvironment that accompany the therapeutic effects of the immunocytokine NHS-IL12. J ImmunoTher Cancer. 7(1):150, 2019.
  • Gatti-Mays ME … Schlom J, Gulley JL. A phase 1 dose-escalation trial of BN-CV301, a recombinant poxviral vaccine targeting MUC-1 and CEA with costimulatory molecules. Clin Cancer Res. 25(16):4933-4944, 2019.
  • Allen CT ... Schlom J ... Hinrichs CS. Safety and clinical activity of PD-L1 blockade in patients with aggressive recurrent respiratory papillomatosis. J ImmunoTher Cancer. 7(1):119, 2019.
  • Knudson KM … Schlom J. Mechanisms involved in IL-15 superagonist enhancement of anti-PD-L1 therapy. J ImmunoTher Cancer. 7(1):82, 2019.
  • Sun L … Schlom J … Allen CT. Inhibiting myeloid derived suppressor cell trafficking enhances T cell immunotherapy. JCI Insight. 4(7):e126853, 2019.
  • Friedman J … Schlom J … Allen C. Direct and antibody-dependent cell-mediated cytotoxicity of head and neck squamous cell carcinoma cells by high-affinity natural killer cells. Oral Oncol. 90:38-44, 2019.
  • Karzai F … Schlom J … Dahut WL. Activity of durvalumab plus olaparib in metastatic castration-resistant prostate cancer in men with and without DNA damage repair mutations. J Immunother Cancer. 6:141, 2018.
  • Parsons JK … Schlom J … Chow HS. A randomized, double-blind, phase II trial of PSA-TRICOM (PROSTVAC) in patients with localized prostate cancer: the immunotherapy to prevent progression on active surveillance study. Eur Urol Focus. 4(5):636-638, 2018.
  • Jochems C ... Schlom J. The multi-functionality of N-809, a novel fusion protein encompassing anti-PD-L1 and the IL-15 superagonist fusion complex. OncoImmunology. 8(2);e1532764, 2018.
  • Schlom J and Gulley JL. Vaccines as an integral component of cancer immunotherapy (Viewpoint). JAMA. 320(21):2195-2196, 2018.
  • Mammen AL … Schlom J, Gulley JL. Preexisting antiacetylcholine receptor autoantibodies and B cell lymphopenia are associated with the development of myositis in thymoma patients treated with avelumab, an immune checkpoint inhibitor targeting programmed death-ligand 1. Ann Rheum Dis. 8(1):150-152, 2019.
  • Strauss J … Schlom J, Gulley JL. First-in-human phase I trial of a tumor-targeted cytokine (NHS-IL12) in subjects with metastatic solid tumors. Clin Cancer Res. 25(1):99-109, 2019.
  • McGee HM…Schlom J … Monjazeb AM. Stereotactic ablative radiation therapy induces systemic differences in peripheral blood immunophenotype dependent on irradiated site. Int J Radiat Oncol Biol Phys. 101(5):1259-1270, 2018.
  • Friedman J … Schlom J … Allen CT. Inhibition of WEE1 kinase and cell cycle checkpoint activation sensitizes head and neck cancers to natural killer cell therapies. J ImmunoTher. Cancer, 6:59, 2018.
  • Merino MJ … Schlom J, Gulley JL. Morphological changes induced by intraprostatic PSA-based vaccine in prostate cancer biopsies (phase I clinical trial). Hum Pathol. 78:72-78, 2018.
  • Hicks KC … Schlom J. Epigenetic priming of both tumor and NK cells augments antibody-dependent cellular cytotoxicity elicited by the anti-PD-L1 antibody avelumab against multiple carcinoma cell types. OncoImmunology. 7(11):e1466018, 2018.
  • Knudson KM ... Schlom J. M7824, a novel bifunctional anti-PD-L1/TGFβ Trap fusion protein, promotes anti-tumor efficacy as monotherapy and in combination with vaccine. OncoImmunology. 7(5):e1426519, 2018.
  • Fujii R ... Schlom J, Hodge JW. An IL-15 superagonist/IL-15Rα fusion complex protects and rescues NK cell cytotoxic function from TGF-β1-mediated immunosuppression. Cancer Immunol Immunother. 67(4):675-689, 2018.
  • Strauss J ... Schlom J ... Gulley JL. Phase 1 trial of M7824 (MSB0011359C), a bifunctional fusion protein targeting PD-L1 and TGF-β, in advanced solid tumors. Clin Cancer Res. 24(6):1287-1295, 2018.
  • Grenga I ... Schlom J. Anti-PD-L1/TGFβR2 (M7824) fusion protein induces immunogenic modulation of human urothelial carcinoma cell lines, rendering them more susceptible to immune-mediated recognition and lysis. Urol Oncol. 36(3):93.e1-93.311, 2018.
  • Jochems C … Schlom J. Analyses of functions of an anti-PD-L1/TGFβR2 bispecific fusion protein (M7824). Oncotarget. 8:75217-75231, 2017.
  • Heery CR...Gulley JL, Schlom J. Phase I study of a poxviral TRICOM-based vaccine directed against the transcription factor brachyury. Clin Cancer Res. 23:6833-45, 2017.
  • David JM...Schlom J, Palena C. A novel bifunctional anti-PD-L1/TGF-β Trap fusion protein (M7824) efficiently reverts mesenchymalization of human lung cancer cells. OncoImmunology. 6(10):e1349589, 2017.
  • Tsang KY...Schlom J. Identification and characterization of enhancer agonist human cytotoxic T-cell epitopes of the human papillomavirus type 16 (HPV16) E6/E7. Vaccine. 35:2605-11, 2017.
  • Fallon JK…Greiner JW, Schlom J. Enhanced antitumor effects by combining an IL-12/anti-DNA fusion protein with avelumab, an anti-PD-L1 antibody. Oncotarget. 8:20558-71, 2017.
  • Donahue RN...Gulley JL, Schlom J. Analyses of the peripheral immunome following multiple administrations of avelumab, a human IgG1 anti-PD-L1 monoclonal antibody. J ImmunoTher Cancer 5:20, 2017.
  • Heery CR…Schlom J, Gulley JL. Avelumab for metastatic or locally advanced previously treated solid tumours (JAVELIN Solid Tumor): a phase 1a, multicohort, dose-escalation trial. Lancet Oncol. 18:587-98, 2017.
  • Jochems C...Schlom J. An NK cell line (haNK) expressing high levels of granzyme and engineered to express the high affinity CD16 allele. Oncotarget 7:86359-73, 2016.
  • Farsaci B… Gulley JL, Schlom J. Analyses of pre-therapy peripheral immunoscore and response to vaccine therapy. Cancer Immunol Res. 4:755-65, 2016.
  • Vandeveer AJ…Greiner JW, Schlom J. Systemic immunotherapy of non–muscle invasive mouse bladder cancer with avelumab, an anti–PD-L1 immune checkpoint inhibitor. Cancer Immunol Res. 4:452-62, 2016.
  • Kim PS…Hodge JW, Schlom J. IL-15 superagonist/IL-15RαSushi-Fc fusion complex (IL-15SA/IL-15RαSu-Fc; ALT-803) markedly enhances specific subpopulations of NK and memory CD8+ T cells, and mediates potent anti-tumor activity against murine breast and colon carcinomas. Oncotarget. 7:16130-45, 2016.
Position Degree Required Contact Name E-mail Address
Post-doctoral Fellow - immunology, immunotherapy Ph.D. or equivalent, M.D. or equivalent Jeffrey Schlom js141c@nih.gov

In Viewpoint: Evolving Issues in Oncology: “Vaccines as an integral component of cancer immunotherapy,” Drs. Jeffrey Schlom and James Gulley describe the opportunities and challenges for vaccine therapies to treat cancers.  JAMA. 2018 Dec 4;320(21):2195-2196.

https://www.ncbi.nlm.nih.gov/pubmed/30419097

https://jamanetwork.com/journals/jama/fullarticle/2714651

 

 

About

Mission

The Laboratory of Tumor Immunology and Biology (LTIB) functions as a multidisciplinary and interdisciplinary translational research programmatic effort with the goal of developing novel immunotherapies for cancer. The LTIB strategic plan focuses on the development of novel immunotherapeutics, not only as monotherapies, but more importantly, in combination with other immune-mediating modalities, and other conventional or experimental therapies, as part of an immuno-oncology programmatic effort. Within this effort are several research groups and a clinical trials group, and multiple collaborations with intramural and extramural scientific and clinical investigators, and with investigators in the private sector.

Organization

Office of the Chief:  Dr. Jeffrey Schlom (Senior Investigator, Laboratory Chief). This office is responsible for the administrative functions of the LTIB, such as travel, personnel actions, training, meetings, manuscript editing, purchasing, etc.

Immunoregulation Group:  Dr. Claudia Palena (Senior Investigator, Section Head). This group investigates mechanisms of tumor progression, including mechanisms of metastasis and tumor resistance to therapies, and how immune-based therapies can be employed as therapeutics directed against such tumor-cell phenotypes. These studies have led to the identification and analyses of transcription factors that are drivers of the phenomenon of epithelial-to-mesenchymal transition (EMT) and to ongoing clinical studies employing vaccines directed against one of these gene products.

Recombinant Vaccine Group:  Dr. James Hodge (Senior Investigator, Section Head). This group investigates how non-immune-based therapies affect tumor cells and specific components of the immune system. An emphasis is placed on the mechanisms of how standard-of-care and new experimental therapies alter tumor cells to render them more susceptible to immune-based therapies. These studies form the rationale for novel immune- and non-immune-based combination clinical trials.

Immunomodulation Group: Dr. Sofia Gameiro (Staff Scientist, Group Head). This group examines how emerging therapeutics can modulate the immune system to exert potent antitumor activity, with particular emphasis on how the mechanisms involved can be exploited to maximize antitumor activity in combination regimens with novel immunotherapies and other anticancer modalities. These studies form the rationale for novel hypothesis-driven clinical interventions.

Cytokine Group:  Dr. John Greiner (Staff Scientist, Group Head). This group investigates the mechanisms by which cytokines and other immune modulators affect the host immune system and the tumor microenvironment for use in combination with immunotherapeutics and other forms of cancer therapy.

Cellular Immunology Group:  Dr. Caroline Jochems Frohlich (Staff Scientist, Group Head). This group is involved in studies to identify and modify tumor-associated antigens to enhance their immunogenicity in cancer patients in vaccine-mediated immunotherapy. The group also studies patients' immune responses to provide critical information toward the development of more effective immunotherapeutic approaches to cancer.

Molecular Immunology Group:  Dr. Renee Donahue (Staff Scientist, Group Head). In this group emphasis is placed on the identification of specific immune cell subsets that can help identify cancer patients most likely to benefit from immunotherapy. This group also studies the tumor microenvironment and specific immune cell subsets in the periphery, pre- and post-immunotherapy, to identify potential correlations with clinical responses of patients treated with immunotherapies as monotherapy or combination therapy.

Immunotherapeutics Group:  Dr. Duane Hamilton (Staff Scientist, Group Head). This group focuses on the identification and characterization of tumor-specific antigens and neoepitopes. This group evaluates techniques to identify tumor antigens unique to a patient’s own tumor. It is this group's belief that vaccinating patients with neoepitopes uniquely expressed by their tumor will improve the breadth of anti-tumor immunity generated by the lab's vaccine platforms, and result in greater immunological control of tumor growth.

Clinical Trials Group: Dr. Julius Strauss (Assistant Research Physician, Group Director). This group designs and conducts science-driven clinical studies as a consequence of hypothesis-driven preclinical studies in the laboratory. Dr. Strauss works closely with the following oncologists who also have joint appointments in the LTIB: Drs. James Gulley, Ravi MadanJason RedmanMarijo Bilusic and Fatima Karzai (Genitourinary Malignancies Branch); with Dr. Margaret Gatti-Mays (Division of Medical Ocology, The James Cancer Hospital and The Ohio State Comprehensive Cancer Center), a Special Volunteer at the NIH; and with Dr. Schlom and other LTIB staff members as a well-integrated immunotherapy team. This group also serves as the conduit for collaborative trials with clinical investigators in other NCI Branches and at numerous extramural Cancer Centers.

STRATEGIC PLAN

The LTIB program takes advantage of the uniqueness of the NCI intramural program in that it spans high-risk basic discovery research in immunology and tumor biology, through preclinical translational research, to paradigm-shifting clinical trials. Focus is placed on the design and development of novel 'off-the-shelf' recombinant immunotherapeutics and immunomodulators that can be used in clinical studies at numerous institutions, and do not involve costly and labor-intensive ex vivo manipulations that can be carried out in only one or two centers. This is accomplished in part via Cooperative Research and Development Agreements (CRADAs) with partners in the private sector. The immunotherapeutics and immune modulators that we have developed have also enabled multiple collaborations with clinical investigators at extramural Cancer Centers.

While the use of checkpoint inhibitor monoclonal antibodies (MAb) has shown clear clinical benefit in patients with melanoma, and some other malignancies, in the vast majority of solid tumors <20% of patients benefit from this class of therapies. The LTIB has been and is involved in the design and development of a spectrum of immunotherapeutic and immunomodulatory agents. Preclinical studies have been completed or are ongoing with a range of agents, and clinical studies using many of these agents as monotherapies or in combination therapies are either completed, ongoing or planned to begin shortly.

The preclinical and clinical immunotherapy studies employing a spectrum of different immunotherapeutic agents including vaccines, checkpoint inhibitors, immune modulators, and inhibitors of immune suppressive entities have the potential to convert tumors that currently do not respond to checkpoint inhibition monotherapy (so-called “cold tumors”) into permissive immunogenic targets leading to clinical benefit in patients with multiple types of tumors. A major emphasis of these studies is to also better understand the mechanisms of both host immune cell activation and resistance of tumors to immunotherapeutic approaches, both within the tumor microenvironment and in the peripheral immunome. It may also define which patients will respond to combination immunotherapies when interrogated either (a) prior to the initiation of treatment or (b) early in the therapeutic regimen. These studies may also define which patients will most likely develop autoimmune events when the peripheral immunome is interrogated either prior to the initiation of therapy or early in the therapeutic regimen.

Agents Under Preclinical and Clinical Investigation as Monotherapy or in Combination Therapies Are:

  • Recombinant vaccines: (a) Poxviral vectors expressing three costimulatory molecules and expressing transgenes for either PSA, CEA plus MUC1, or brachyury. The transcription factor brachyury has been identified as a driver of the epithelial-to-mesenchymal transition (EMT) process, stemness, and resistance to therapy. (b) Admixtures of proprietary recombinant adenovirus vectors containing transgenes for brachyury, CEA, MUC1, PSA, and tumor neoepitopes.
  • Checkpoint inhibitors: (a) anti-PDL1 (avelumab) and (b) anti-PDL1/TGF-betaR2 (TRAP).
  • Immune enhancers: (a) IL-15/Ra/Fc immunocytokine (Alt-803), (b) tumor targeting IL-12 immunocytokine (NHS-IL12), and (c) IDO inhibitor.
  • Costimulators: agonist antibodies to OX40, 41BB, and GITR.
  • Inhibitors of immune suppressive entities: (a) anti-IL8 MAb, (b) small molecule IL-8 inhibitor (IL-8 receptor antagonist), and (c) anti-PDL1/TGF-betaR2 (TRAP).

 

Clinical Trials Ongoing, Recently Completed or In Review Involving LTIB Activities:

The major goals of these studies are (a) to conduct science-driven clinical studies of specific immunotherapeutics based on hypothesis-generated preclinical experimentation, and (b) to conduct "proof of concept" clinical studies employing specific immunotherapeutics as part of an immuno-oncology platform. There are four major components to LTIB clinical trials: (a) preclinical studies providing the rationale, (b) preparation of INDs and protocols, etc., and appropriate reviews, (c) the clinical trials, and (d) analyses of patients' immune responses and clinical correlates. Collaborative clinical studies are also ongoing with clinical investigators in the LTIB and in several other Branches of the Center for Cancer Research, NCI, and with clinicians at several extramural Cancer Centers.

Ongoing intramural clinical trials:

  • Phase I/II trial of combination immunotherapy in subjects with advanced HPV associated malignancies (PDS0101+M7824+M9241) (PI, Strauss)
  • Phase II trial of M7824 in subjects with HPV positive malignancies (PI, Strauss)
  • First-in-human Phase I trial of NHS-IL12 in subjects with metastatic solid tumors (PI, Gulley)
  • A Phase I, open-label, multiple-ascending dose trial to investigate the safety, tolerability, pharmacokinetics, biological and clinical activity of avelumab (MSB0010718C), a monoclonal anti-PD-L1 antibody, in subjects with metastatic or locally advanced solid tumors and expansion to selected indications (PI, Gulley)
  • A Phase Ib open label, dose finding trial to evaluate the safety, tolerability, and pharmacokinetics of avelumab in combination with M9241 (NHS-IL12) in subjects with locally advanced, unresectable, or metastatic solid tumors (PI, Gulley)
  • A Phase I/II study of immunotherapy combination BN-brachyury vaccine, M7824, ALT-803 and Epacadostat (QuEST1) (PI, Gulley)
  • Phase I Study of PROSTVAC in combination with nivolumab in men with prostate cancer (PI, Gulley)
  • Phase II trial of combination immunotherapy (Prostvac, CV301 and M7824) in biochemically recurrent prostate cancer (PI, Madan)
  • Phase I open label trial of intravenous administration of MVA-BN-brachyury vaccine in patients with advanced cancer (PI, Bilusic)
  • A pilot study to investigate the safety and clinical activity of avelumab (MSB0010718C) in thymoma and thymic carcinoma after progression on platinum-based chemotherapy (PI, Rajan)
  • Phase IB/II single-arm study of M7824 in with gemcitabine in adults with previously treated advanced adenocarcinoma of the pancreas (PI, Rudloff)
  • Phase II trial of a combination of ATR inhibitor M-6220 and low-dose topotecan with M7824, a novel bifunctional fusion protein targeting PD-L1 and TGF-β pathways in small cell cancers (PI, Thomas/Pommier)
  • A Phase I study of interleukin-15 in combination with avelumab (Bavencio) in relapsed/refractory mature t-cell malignancies (PI, Miljkovic)
  • A phase II pilot study of avelumab in combination with hypofractionated radiotherapy in patients with relapsed refractory multiple myeloma (PI, Kazandijan)
  • Phase II trial of avelumab (Bavencio®) with IL-15 in subjects with clear-cell renal carcinoma (PI, Waldmann/Conlan)

Ongoing extramural clinical trials:

  • A phase II trial of avelumab a fully humanized antibody that target cells expressing PDL1 in patients with recurrent or progressive osteosarcoma (St Jude’s, PI, Bishop)
  • A phase II trial of perioperative CV301 Vaccination in Combination with Nivolumab and Systemic Chemotherapy for Resectable Hepatic-limited metastatic colorectal cancer (Rutgers, PI, Carpizo)
  • A phase I/II trial of the PD-L1 inhibitor, durvalumab (MEDI4736) plus CV301 in combination with maintenance chemotherapy for patients with metastatic colorectal or pancreatic adenocarcinoma (Georgetown University, PI, Pishvaian/Weinberg)
  • OXEL: A pilot study of immune checkpoint or capecitabine or combination therapy as adjuvant therapy for triple negative breast cancer with residual disease following neoadjuvant chemotherapy (Georgetown University, PI, Lynce)
  • A pilot trial of induction talazoparib followed by combination of talazoparib and avelumab in advanced breast cancer: the TALAVE study (Georgetown University, PI, Lynce)
  • Phase II randomized, placebo-controlled trial of PROSTVAC (PSA-TRICOM) in patients with clinically localized prostate cancer undergoing active surveillance (University of Arizona, PI, Chow)

Completed clinical trials:

  • A randomized Phase II trial of standard of care alone or in combination with Ad-CEA vaccine and avelumab in patients with previously untreated metastatic colorectal cancer (PI, Strauss)
  • CV301 Single Patient Study (PI, Gatti-Mays)
  • A Phase I, open-label, multiple-ascending dose trial to investigate the safety, tolerability, pharmaco-kinetics, biological and clinical activity of MSB0011359C (M7824) in subjects with metastatic or locally advanced solid tumors with expansion to selected indications (PI, Gulley)
  • A randomized phase II trial combining vaccine therapy with PROSTVAC /TRICOM and enzalutamide vs. enzalutamide alone in men with metastatic castration resistant prostate cancer (PI, Madan)
  • Docetaxel and PROSTVAC for metastatic castration sensitive prostate cancer (PI, Madan)
  • Open-label phase II trial to evaluate the safety and tolerability of MVA priming and fowlpox booster (MVA-BN-brachyury/FPV-brachyury) (PI, Bilusic)
  • Treatment of patients with castration resistant prostate cancer using multi-targeted recombinant Ad5 PSA/MUC1/brachyury based immunotherapy vaccines (PI, Bilusic)
  • A phase II study of M7824 in subjects with recurrent respiratory papillomatosis (PI, Hinrichs)
  • Phase I trial using a multi-targeted recombinant Ad5 (CEA/MUC1/Brachyury)–based immunotherapy vaccine regimen in patients with advanced cancer (PI, Strauss)
  • A CV301 phase 1/1b study followed by randomized phase 2 study of CV301 in combination with nivolumab versus nivolumab in subjects with previously treated non-small cell lung cancer (PI, Gulley)
  • A randomized, double-blind, Phase 2 trial of GI-6301 (yeast-brachyury vaccine) versus placebo in combination with standard of care definitive radiotherapy in locally advanced, unresectable, chordoma (PI, Gulley)
  • A phase II trial of enzalutamide in combination with PSA-TRICOM in patients with non-metastatic castration sensitive prostate cancer (PI, Madan)
  • Prostvac in patients with biochemical recurrent prostate cancer (PI, Madan)
  • A phase I study of avelumab in subjects with recurrent respiratory papillomatosis (PI, Hinrichs)
  • A phase II, open-label, multicenter trial to investigate the clinical activity and safety of MSB0010718C in subjects with merkel cell carcinoma (PI, Brownell)

Clinical trials in review:

  • BrEAsT: A phase Ib trial of sequential combinations of BN-brachyury, entinostat, ado-trastuzumab emtansine and M7824 in advanced stage breast cancer (PI, Gatti-Mays)
  • An open-label, Phase I dose-escalation study investigating the safety, tolerability, pharmacokinetics, biological and clinical activity of M6903 (anti-TIM3 antibody) in combination with M7824 in subjects with advanced solid tumors (PI, Redman)
  • A phase I study of TGF-β trap (M7824) and NHS-IL12 (M9241) alone and in combination with stereotactic body radiation therapy (SBRT) in adults with metastatic non-prostate genitourinary malignancies (PI, Apolo)
  • Retrospective study of M7824 related adverse effects in adults with cancer (PI, Brownell)
  • Phase I/II of NHS-IL12 monotherapy and in combination with M7824 in advanced Kaposi sarcoma (PI, Yarchoan)
  • QUICC: Phase II trial of combination immunotherapy in subjects with advanced small bowel and colorectal cancers (PI, Strauss)
  • WOOT: Phase I/II trial of HPV vaccine PRGN-2009 alone or in combination with anti-PD-L1/TGFß trap (M7824) in subjects with HPV positive cancers (PI, Strauss)
  • STAT: Phase I/II trial investigating the safety, tolerability, pharmacokinetics, immune and clinical activity of SX-682 in combination with Bintrafusp alfa (M7824 or TGF-b “trap”/PD-L1) with BN-CV301 TRICOM in advanced solid tumors (PI, Gatti-Mays)
  • ABC trial: abemaciclib + M7824 + CV301 +- N-803 in HR+ breast cancer (PI Gatti-Mays)
  • A phase I/II study of PD-L1 t-haNK cells plus Immunotherapy in Subjects with Advanced Cancer (PI, Redman)
  • A sequential window of opportunity trial of anti-PD-L1/TGF-β trap (M7824) alone and in combination with TriAd vaccine, and N-803 for p16-negative resectable head and neck squamous cell carcinoma (PI, Redman)
  • Chemoimmunotherapy of prostate cancer mCRPC and mCSPC (docetaxel + ADT + M7824 + M9241) (PI, Madan)
  • A phase 1/2, open-label, dose-escalation, safety and tolerability study of NC410 in subjects with advanced or metastatic solid tumors (PI, Bilusic)
  • BEST: phase I/II trial of the combination of Bintrafusp alfa (M7824), entinostat and NHS-IL12 (M9241) in patients with advanced cancer (PI, Sater)
  • Phase 2 study of Bintrafusp alpha in recurrent/metastatic olfactory neuroblastoma (BARON) (PI, Floudas)
  • A phase II, open-label trial of Bintrafusp alfa (M7824) in subjects with thymoma and thymic carcinoma (PI, Rajan)

 

Recent Selected Publications:

  • Strauss J … Schlom J, Gulley JL. Bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with human papillomavirus–associated malignancies. J Immunother Cancer (in press)
  • Smalley Rumfield C … Schlom J. Therapeutic vaccines for HPV-associated malignancies (review). ImmunoTargets Ther (in press).
  • Schlom J and Donahue RN. The importance of cellular immunity in the development of vaccines and therapeutics for COVID-19 (Perspective). J Infect Dis. 222(9):1435-1438, 2020.
  • Lee KL, Schlom J, Hamilton DH. Combination therapies utlizing neoepitope-targeted vaccines (review). Cancer Immunol Immunother (in press).
  • Morillon II YM … Schlom J. The development of next-generation PBMC humanized mice for preclinical investigation of cancer immunotherapeutic agents. Anticancer Res. 40: 5329-5341, 2020.
  • Robbins Y… Schlom J, Hodge JW, Allen CT. Tumor control targeting PD-L1 with chimeric antigen receptor modified NK cells. eLife. 9:e54854, 2020.
  • Del Rivero J … Schlom J, Gulley JL, Madan RA. A case report of sequential use of a yeast-CEA therapeutic cancer vaccine and anti-PD-L1 inhibitor in metastatic medullary thyroid cancer. Front Endocrinol. 11:490, 2020.
  • Fabian KP … Schlom J, Hodge. PD-L1-targeting high-affinity NK cells (PD-L1 t-haNK) induce direct antitumor effects and target suppressive MDSC populations. J Immunother Cancer 8(1):e000450, 2020.
  • Smalley Rumfield C … Schlom J. Immunomodulation to enhance the efficacy of an HPV therapeutic vaccine. J Immunother Cancer. 8(1):e000612, 2020.
  • Solocinski K … Schlom J, Hodge JW. Overcoming hypoxia-induced functional suppression of NK cells. J Immunother Cancer 8(1) e000246, 2020.
  • Morillon II YM … Schlom J. The use of a humanized NSG-β2m−/− model for investigation of immune and anti-tumor effects mediated by the bifunctional immunotherapeutic bintrafusp alfa. Front Oncol. 10:549, 2020.
  • Knudson KM ... Schlom J, Gameiro SR. Rationale for IL-15 superagonists in cancer immunotherapy. Exp Op Biol Ther. 11:1-5, 2020.
  • Knudson KM … Schlom J. Functional and mechanistic advantage of the use of a bifunctional anti-PD-L1/IL-15 superagonist. J Immunother Cancer 8(1):e00049, 2020.
  • Abdul Sater H … Schlom J … Gulley JL. Neoadjuvant PROSTVAC prior to radical prostatectomy enhances T-cell infiltration into the tumor immune microenvironment in men with prostate cancer. J Immunother Cancer 8(1):e000655, 2020.
  • Horn LA … Schlom J, Palena C. Simultaneous inhibition of CXCR1/2, TGF-β, and PD-L1 remodels the tumor and its microenvironment to drive anti-tumor immunity. J Immunother Cancer 8(1):e000326, 2020.
  • Lind H … Schlom J. Dual targeting of TGF-β and PD-L1 via a bifunctional anti-PD-L1/TGF-βRII agent: status of preclinical and clinical advances. [review] J Immunother Cancer 8(1):e000433, 2020.
  • Greene S … Schlom J … Allen C. Inhibition of myeloid cell trafficking with dual CXCR1 and CXCR2 blockade enhances NK cell immunotherapy. Clin Cancer Res. 26:1420-1431, 2020.
  • Collins JM … Schlom J, Gulley JL, Bilusic M. Phase I trial of a modified vaccinia Ankara (MVA) priming vaccine followed by a fowlpox virus (FPV) boosting vaccine modified to express brachyury and costimulatory molecules in advanced solid tumors. The Oncologist. 25(7):560-e1006, 2020.
  • Giles AJ … Schlom J … Park DM. Efficient ADCC-killing of meningioma by avelumab and a high-affinity natural killer cell line, haNK. JCI Insight. 4(20), 2019.
  • Hicks KC … Schlom J. Cooperative immune-mediated mechanisms of the HDAC inhibitor entinostat, an IL-15 superagonist, and a cancer vaccine effectively synergize as a novel cancer therapy. Clin Cancer Res. 26:704-716, 2020.
  • Rajan A … Schlom J … Gulley JL. Efficacy and tolerability of anti-programmed death-ligand 1 (PD-L1) antibody (avelumab) treatment in advanced thymoma. J ImmunoTher Cancer. 7(1):269, 2019.
  • Bilusic M … Schlom J, Gulley JL. Phase I trial of HuMax-IL8 (BMS-986253), an anti-IL-8 monoclonal antibody, in patients with metastatic or unresectable solid tumors. J Immunother Cancer 7(1):240, 2019.
  • Gatti-Mays ME … Schlom J … Strauss J. A phase I trial using a multi-targeted recombinant Ad5 (CEA/MUC1/Brachyury)–based immunotherapy vaccine regimen in patients with advanced cancer. The Oncologist [Clinical Trial Results Section]. 24:1-6, 2020.
  • Lee KL … Schlom J. Efficient tumor clearance and diversified immunity through neoepitope vaccines and combinatorial immunotherapy. Cancer Immunol Res. 7:1359-1370, 2019.
  • Morillon YM … Schlom J. Temporal changes within the (bladder) tumor microenvironment that accompany the therapeutic effects of the immunocytokine NHS-IL12. J ImmunoTher Cancer. 7(1):150, 2019.
  • Gatti-Mays ME … Schlom J, Gulley JL. A phase 1 dose-escalation trial of BN-CV301, a recombinant poxviral vaccine targeting MUC-1 and CEA with costimulatory molecules. Clin Cancer Res. 25(16):4933-4944, 2019.
  • Allen CT ... Schlom J ... Hinrichs CS. Safety and clinical activity of PD-L1 blockade in patients with aggressive recurrent respiratory papillomatosis. J ImmunoTher Cancer. 7(1):119, 2019.
  • Knudson KM … Schlom J. Mechanisms involved in IL-15 superagonist enhancement of anti-PD-L1 therapy. J ImmunoTher Cancer. 7(1):82, 2019.
  • Sun L … Schlom J … Allen CT. Inhibiting myeloid derived suppressor cell trafficking enhances T cell immunotherapy. JCI Insight. 4(7):e126853, 2019.
  • Friedman J … Schlom J … Allen C. Direct and antibody-dependent cell-mediated cytotoxicity of head and neck squamous cell carcinoma cells by high-affinity natural killer cells. Oral Oncol. 90:38-44, 2019.
  • Karzai F … Schlom J … Dahut WL. Activity of durvalumab plus olaparib in metastatic castration-resistant prostate cancer in men with and without DNA damage repair mutations. J Immunother Cancer. 6:141, 2018.
  • Parsons JK … Schlom J … Chow HS. A randomized, double-blind, phase II trial of PSA-TRICOM (PROSTVAC) in patients with localized prostate cancer: the immunotherapy to prevent progression on active surveillance study. Eur Urol Focus. 4(5):636-638, 2018.
  • Jochems C ... Schlom J. The multi-functionality of N-809, a novel fusion protein encompassing anti-PD-L1 and the IL-15 superagonist fusion complex. OncoImmunology. 8(2);e1532764, 2018.
  • Schlom J and Gulley JL. Vaccines as an integral component of cancer immunotherapy (Viewpoint). JAMA. 320(21):2195-2196, 2018.
  • Mammen AL … Schlom J, Gulley JL. Preexisting antiacetylcholine receptor autoantibodies and B cell lymphopenia are associated with the development of myositis in thymoma patients treated with avelumab, an immune checkpoint inhibitor targeting programmed death-ligand 1. Ann Rheum Dis. 8(1):150-152, 2019.
  • Strauss J … Schlom J, Gulley JL. First-in-human phase I trial of a tumor-targeted cytokine (NHS-IL12) in subjects with metastatic solid tumors. Clin Cancer Res. 25(1):99-109, 2019.
  • McGee HM…Schlom J … Monjazeb AM. Stereotactic ablative radiation therapy induces systemic differences in peripheral blood immunophenotype dependent on irradiated site. Int J Radiat Oncol Biol Phys. 101(5):1259-1270, 2018.
  • Friedman J … Schlom J … Allen CT. Inhibition of WEE1 kinase and cell cycle checkpoint activation sensitizes head and neck cancers to natural killer cell therapies. J ImmunoTher. Cancer, 6:59, 2018.
  • Merino MJ … Schlom J, Gulley JL. Morphological changes induced by intraprostatic PSA-based vaccine in prostate cancer biopsies (phase I clinical trial). Hum Pathol. 78:72-78, 2018.
  • Hicks KC … Schlom J. Epigenetic priming of both tumor and NK cells augments antibody-dependent cellular cytotoxicity elicited by the anti-PD-L1 antibody avelumab against multiple carcinoma cell types. OncoImmunology. 7(11):e1466018, 2018.
  • Knudson KM ... Schlom J. M7824, a novel bifunctional anti-PD-L1/TGFβ Trap fusion protein, promotes anti-tumor efficacy as monotherapy and in combination with vaccine. OncoImmunology. 7(5):e1426519, 2018.
  • Fujii R ... Schlom J, Hodge JW. An IL-15 superagonist/IL-15Rα fusion complex protects and rescues NK cell cytotoxic function from TGF-β1-mediated immunosuppression. Cancer Immunol Immunother. 67(4):675-689, 2018.
  • Strauss J ... Schlom J ... Gulley JL. Phase 1 trial of M7824 (MSB0011359C), a bifunctional fusion protein targeting PD-L1 and TGF-β, in advanced solid tumors. Clin Cancer Res. 24(6):1287-1295, 2018.
  • Grenga I ... Schlom J. Anti-PD-L1/TGFβR2 (M7824) fusion protein induces immunogenic modulation of human urothelial carcinoma cell lines, rendering them more susceptible to immune-mediated recognition and lysis. Urol Oncol. 36(3):93.e1-93.311, 2018.
  • Jochems C … Schlom J. Analyses of functions of an anti-PD-L1/TGFβR2 bispecific fusion protein (M7824). Oncotarget. 8:75217-75231, 2017.
  • Heery CR...Gulley JL, Schlom J. Phase I study of a poxviral TRICOM-based vaccine directed against the transcription factor brachyury. Clin Cancer Res. 23:6833-45, 2017.
  • David JM...Schlom J, Palena C. A novel bifunctional anti-PD-L1/TGF-β Trap fusion protein (M7824) efficiently reverts mesenchymalization of human lung cancer cells. OncoImmunology. 6(10):e1349589, 2017.
  • Tsang KY...Schlom J. Identification and characterization of enhancer agonist human cytotoxic T-cell epitopes of the human papillomavirus type 16 (HPV16) E6/E7. Vaccine. 35:2605-11, 2017.
  • Fallon JK…Greiner JW, Schlom J. Enhanced antitumor effects by combining an IL-12/anti-DNA fusion protein with avelumab, an anti-PD-L1 antibody. Oncotarget. 8:20558-71, 2017.
  • Donahue RN...Gulley JL, Schlom J. Analyses of the peripheral immunome following multiple administrations of avelumab, a human IgG1 anti-PD-L1 monoclonal antibody. J ImmunoTher Cancer 5:20, 2017.
  • Heery CR…Schlom J, Gulley JL. Avelumab for metastatic or locally advanced previously treated solid tumours (JAVELIN Solid Tumor): a phase 1a, multicohort, dose-escalation trial. Lancet Oncol. 18:587-98, 2017.
  • Jochems C...Schlom J. An NK cell line (haNK) expressing high levels of granzyme and engineered to express the high affinity CD16 allele. Oncotarget 7:86359-73, 2016.
  • Farsaci B… Gulley JL, Schlom J. Analyses of pre-therapy peripheral immunoscore and response to vaccine therapy. Cancer Immunol Res. 4:755-65, 2016.
  • Vandeveer AJ…Greiner JW, Schlom J. Systemic immunotherapy of non–muscle invasive mouse bladder cancer with avelumab, an anti–PD-L1 immune checkpoint inhibitor. Cancer Immunol Res. 4:452-62, 2016.
  • Kim PS…Hodge JW, Schlom J. IL-15 superagonist/IL-15RαSushi-Fc fusion complex (IL-15SA/IL-15RαSu-Fc; ALT-803) markedly enhances specific subpopulations of NK and memory CD8+ T cells, and mediates potent anti-tumor activity against murine breast and colon carcinomas. Oncotarget. 7:16130-45, 2016.

Clinical Trials

PI & Key Staff

Positions

Position Degree Required Contact Name E-mail Address
Post-doctoral Fellow - immunology, immunotherapy Ph.D. or equivalent, M.D. or equivalent Jeffrey Schlom js141c@nih.gov

Contact Info

Laboratory of Tumor Immunology and Biology
Center for Cancer Research
National Cancer Institute
Building 10, Room 8B09
Bethesda, MD 20892-1750
Ph: 240-858-3463
Fax: 240-541-4558
Editor
240-858-3464
Program Manager
240-858-3462
Program Specialist
240-858-3459