Jeffrey  Schlom, Ph.D.
Jeffrey Schlom, Ph.D.
Chief
Senior Investigator

Center for Cancer Research
National Cancer Institute

Building 10, Room 8B09
Bethesda, MD 20892-1750
301-496-4343

As Chief of the Laboratory of Tumor Immunology and Biology, Dr. Schlom directs a translational research program in cancer immunotherapy. He has pioneered the use of novel immunotherapeutics, both as monotherapy and in combination therapies, for a range of human cancers. His studies involve the translation of hypothesis-driven preclinical studies to science-driven clinical trials. Dr. Schlom’s studies involve the design and development of novel therapeutic cancer vaccines, immunocytokines, and checkpoint inhibitor monoclonal antibodies.

Areas of Expertise
1) immunotherapy 2) vaccines 3) checkpoint inhibitors 4) cancer immunology 5) carcinoma therapy

The Laboratory of Tumor Immunology and Biology (LTIB), CCR, is a multidisciplinary and interdisciplinary translational research programmatic effort with the goal of developing novel immunotherapies for cancer. Within this effort are several research groups, a clinical trials group, two independent tenure track investigators, and multiple collaborations with intramural and extramural scientific and clinical investigators, and with investigators in the private sector. The program takes advantage of the uniqueness of the NCI intramural program in that it spans high-risk basic discovery research in immunology, through preclinical translational research, to paradigm-shifting clinical trials. Focus is placed on the design and development of novel 'off-the-shelf' recombinant vaccines 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. The LTIB strategic plan focuses on the development of novel immunotherapeutics for human carcinomas, 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.

Specifically, my research goals consist of four highly integrated projects:

  1. The design and development of novel immunotherapeutics consisting of recombinant vector-based vaccines and novel immunomodulators such as checkpoint inhibitors and immunocytokines. This is accomplished in collaboration with Cooperative Research and Development Agreements (CRADA) partners in the private sector that provide agents for preclinical studies in appropriate animal models that we have developed, and in our preclinical human in vitro systems. These studies in turn provide the rationale for science-driven clinical studies.
     
  2. The effect of 'non-immune'‒based therapies on the immune system. Emphasis is placed on the analyses of samples from patients treated with these 'non-immune'‒based therapies. These combined studies provide the scientific rationale for combination clinical trials of immunotherapeutics with standard-of-care therapies or other experimental therapies.
     
  3. Clinical studies of the developed immunotherapeutics as monotherapies or as part of an immuno-oncology platform. Principal Investigators (PIs) and Associate PIs on these trials are Drs. J. Gulley, R. Madan (Genitourinary Malignancies Branch, CCR) and C. Heery, who work closely with me and other LTIB members as a well-integrated immunotherapy team. The 'off-the-shelf' immunotherapeutics that we have developed have also enabled collaborations with clinical investigators at extramural Cancer Centers.
     
  4. The analyses of patients' immune responses post- vs. pre-therapy to identify immune correlates of clinical benefit, and/or to identify those patients most likely to benefit from immunotherapy.

SCIENTIFIC OVERVIEW

Recent Accomplishments/Ongoing Studies

  • We have continued our preclinical and clinical investigations of two diverse recombinant (rec.) vaccine platforms: (a) rec. poxviral vectors employing a rec. vaccinia prime followed by multiple rec. fowlpox booster vaccinations; each vector contains the transgenes for one or more tumor-associated antigens (TAAs) and three T-cell costimulatory molecules (designated  TRICOM); and (b) heat-killed rec. Saccharomyces cerevisiae (yeast) containing TAA protein via the insertion of a yeast plasmid.
  • We have further interrogated the transcription factor brachyury, which is a major driver of the epithelial-to-mesenchymal transition (EMT) process in human carcinoma cells, as a novel vaccine target. These studies were conducted in collaboration with Dr. Palena. A rec. yeast-brachyury vaccine has been developed and a first-in-human clinical trial is underway. A Phase II trial in chordoma patients is planned.
  • The C-terminus of MUC1 (MUC1-C) has been shown by others to be an oncogene and is associated with drug resistance and poor prognosis for a range of human tumors. We have now identified 9 novel CD8 T-cell epitopes of MUC1; most importantly, 7 are in the C-terminus. We have identified and characterized enhancer agonist epitopes for each of the 9 epitopes. A rec. yeast-MUC1(agonist) vector has been developed that efficiently processes the agonist epitopes for T-cell activation.
  • In collaboration with our CRADA partner, we have developed a tumor-targeting immunocytokine. NHS-IL12 is a fully human monoclonal antibody (MAb) that is fused to human IL-12. The agent was designed to reduce the toxicity of rec. IL-12 protein while maintaining its immuno-enhancing properties at the tumor site. We have shown that the immunocytokine has anti-tumor activity in a range of tumor models. We have ongoing the first-in-human clinical trial with NHS-IL12.
  • We have developed, in collaboration with our CRADA partner, an anti-PDL1 MAb that, unlike other anti-PDL1 MAbs, is capable of mediating antibody dependent cell-mediated cytotoxicity (ADCC) of human carcinomas cells. We have initiated a first-in-human clinical trial with this anti-PDL1.
  • We have analyzed over 100 immune cell subsets of peripheral blood mononuclear cells (PBMCs) from cancer patients both prior to and during standard-of-care therapies to determine whether specific regimens are suitable for use in combination with immunotherapeutics.

Clinical oncologists Drs. Gulley, Madan (Genitourinary Malignancies Branch, CCR) and Heery (LTIB) along with clinical fellows work closely with scientists of the LTIB in a well-integrated immunotherapy team.

  • Prior Phase II studies with rV-, rF-PSA-TRICOM (PROSTVAC) vaccine as a monotherapy in patients with metastatic castration-resistant prostate cancer (mCRPC) have led to an ongoing Phase III study. This is a global 3-arm study in patients (n=1,200) with asymptomatic mCRPC who receive (a) PROSTVAC, (b) PROSTVAC + GM-CSF, (c) placebo (empty vector). Accrual is complete. The endpoint is overall survival (OS).
  • In collaboration with Dr. A. Fojo at the CCR, we have evaluated the growth rates of tumors (via serum prostate-specific antigen (PSA)) in patients with mCRPC receiving PROSTVAC vaccine or several different chemotherapy regimens. These studies have revealed that, unlike chemotherapy, vaccine therapy can reduce the tumor growth rate leading to enhanced survival even in the absence of increases in progression-free survival (PFS).
  • We have now completed a safety and feasibility study of combined i.t./s.c. PROSTVAC vaccination in men with locally recurrent or progressive prostate cancer. 19/21 patients developed stable or improved PSA levels.
  • Following LTIB preclinical studies, we have completed a Phase I trial in patients with mCRPC of PROSTVAC vaccination with increasing doses of ipilimumab (anti-CTLA4). The OS of patients was quite favorable compared with a similar mCRPC population receiving PROSTVAC alone in a separate trial. These findings provide evidence for the use of vaccine in combination with checkpoint inhibitors such as anti-PDL1.
  • Two randomized studies have recently been completed employing PROSTVAC with standard-of-care therapies. Patients with non-metastatic CRPC received the testosterone-suppressing agent flutamide ± PROSTVAC. This study provided the rationale for the ongoing trials with enzalutamide plus vaccine (see below). In a second recently accrued trial, patients with mCRPC with bone metastases were randomized to receive the bone-seeking radionuclide Quadramet (Sm-153) ± PROSTVAC.
  • A dual center (NCI and MD Anderson) study that randomized patients with metastatic breast cancer to docetaxel ± PANVAC vaccine (rV-, rF-CEA-MUC1-TRICOM) has recently been completed.
  • We have completed a first-in-human Phase I study of rec. yeast-CEA vaccine in patients with metastatic disease and demonstrated safety to the generation of CEA-specific T-cell responses. This has led to the initiation of a Phase II study in patients with metastatic medullary thyroid cancer.
  • Two randomized clinical studies have been initiated employing the novel FDA-approved androgen blockade agent enzalutamide ± PROSTVAC vaccine. The first is in mCRPC patients with a time-to-progression (TTP) endpoint; the second trial is in non-metastatic patients with rising PSA where changes in PSA velocity at the discontinuation of enzalutamide will be evaluated.
  • A clinical study is ongoing in collaboration with Dr. P. Agarwal in the CCR Urologic Oncology Branch (UOB). BCG failure bladder cancer patients will be randomized to second-line BCG ± PANVAC vaccine. The primary endpoint will be tumor extent and immune infiltrate in pre- vs. post-treatment biopsies.
  • Numerous immune analyses pre- vs. post-treatment have been/are being employed in clinical studies in an attempt to identify which patients would most likely benefit from a given immunotherapy, and to evaluate potential immune correlates of clinical benefit early in the treatment cycle.
  • We have now developed a FACS-based assay using 15-mer peptides reflecting entire TAA gene to simultaneously measure both CD4 and CD8 responses; this assay is not restricted by HLA allele. When sufficient PBMCs were available, we have analyzed the number, phenotype and suppressive function of Tregs and function of natural killer (NK) cells post- vs. pre-vaccination.
  • We have analyzed post- vs. pre-serum samples for a range of cytokines as well as two potential immunomodulatory molecules. We have shown that soluble CD40L (sCD40L) is elevated in the sera of patients with prostate cancer and metastatic breast and lung cancers. In vitro studies demonstrated sCD40L could enrich MDSC and expand Tregs. We also have shown that soluble CD27 (sCD27) sera levels are decreased in carcinoma patients vs. healthy donors. In vitro studies demonstrated that sCD27 provides strong proliferative signals to lymphocytes.
  • We have used the multi-color FACS-based assay to define a “peripheral immunoscore” monitoring immune cell subsets known in the literature to have specific immune stimulatory or regulatory functions.
  • We have established a collaboration with Epic Sciences, which has a proprietary method to analyze multiple markers in circulating tumor cells (CTC) in a fixed cytologic platform. This will be especially important in analyzing changes in the expression of brachyury, and mesenchymal and epithelial markers in the same CTCs post- vs. pre-therapy.

ADMINISTRATIVE OVERVIEW

I am involved in the training of numerous postdoctoral and clinical fellows, and medical, college and high school students. I take mentoring very seriously, with frequent meetings with postdoctoral and clinical fellows and with Group Heads. Frequent meetings are held to plan experiments, review and discuss data, and to discuss future plans. Meetings are also held to discuss the preparation of oral presentations, poster presentations, and the writing of manuscripts. All laboratory members attend more formal weekly lab meetings in which planned and ongoing research is discussed. There are also invited seminar speakers, and attendance at the numerous seminars ongoing at the NIH is encouraged.

PROTOCOLS IN PROGRESS AT THE NIH CLINICAL CENTER EMPLOYING LTIB AGENTS AND/OR LTIB IMMUNE MONITORING

  • A randomized, double-blind, phase III efficacy trial of PROSTVAC-V/F ±   GM-CSF in men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer
  • A randomized phase II trial combining vaccine therapy with PROSTVAC / TRICOM and flutamide vs. flutamide alone in men with androgen insensitive non-metastatic (D0.5) prostate cancer
  • A randomized phase II trial combining vaccine therapy with PROSTVAC / TRICOM and enzalutamide vs. enzalutamide alone in men with metastatic castration-resistant prostate cancer
  • A phase II trial of enzalutamide in combination with PSA-TRICOM in patients with non-metastatic castration-sensitive prostate cancer
  • A randomized phase II study of L-BLP25 in combination with standard androgen deprivation therapy and radiation therapy for newly diagnosed high-risk prostate cancer patients
  • A pilot study of recombinant yeast-CEA vaccine in patients with recurrent medullary thyroid cancer
  • First-in-human phase I trial of NHS-IL12 in subjects with metastatic solid tumors
  • A randomized prospective phase II study to determine the efficacy of Bacillus Calmette-Guerin (BCG) given in combination with PANVAC versus BCG alone in adults with high grade non-muscle invasive bladder cancer who failed at least 1 induction course of BCG
  • A phase II study of neoadjuvant rFowlpox-PSA (L155)-TRICOM (PROSTVAC-F/TRICOM) in combination with rVaccinia-PSA (L155)-TRICOM (PROSTVAC-V/TRICOM) in men with prostate cancer undergoing treatment with radical prostatectomy
  • An open-label phase I study to evaluate the safety and tolerability of a modified vaccinia Ankara (MVA)–based vaccine modified to express brachyury and T-cell costimulatory molecules (MVA-brachyury-TRICOM)
Scientific Focus Areas:
Cancer Biology, Clinical Research, Immunology, Stem Cell Biology
Selected Publications
  1. Roselli M, Fernando RI, Guadagni F, Spila A, Alessandroni J, Palmirotta R, Costarelli L, Litzinger M, Hamilton DH, Huang B, Tucker JA, Tsang KY, Schlom J, Palena C.
    Clin Cancer Res. 18: 3868-79, 2012. [ Journal Article ]
  2. Gulley JL, Arlen PM, Madan RA, Tsang KY, Pazdur MP, Skarupa L, Jones JL, Poole DJ, Higgins JP, Hodge JW, Cereda V, Vergati M, Steinberg SM, Halabi S, Jones E, Chen C, Parnes H, Wright JJ, Dahut WL, Schlom J.
    Cancer Immunol. Immunother. 59: 663-74, 2010. [ Journal Article ]
  3. Gulley JL, Madan RA, Tsang KY, Jochems C, Marte JL, Farsaci B, Tucker JA, Hodge JW, Liewehr DJ, Steinberg SM, Heery CR, Schlom J.
    Cancer Immunol. Res. 2: 133-141, 2013. [ Journal Article ]
  4. Jochems C, Tucker JA, Tsang KY, Madan RA, Dahut WL, Liewehr DJ, Steinberg SM, Gulley JL, Schlom J.
    Cancer Immunol. Immunother. 63: 407-18, 2014. [ Journal Article ]
  5. Schlom J.
    J. Natl. Cancer Inst. 104: 599-613, 2012. [ Journal Article ]

Dr. Jeffrey Schlom is Chief of the Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH. He received his B.S. from the Ohio State University, M.S. from Adelphi University, and Ph.D. from the Waksman Institute at Rutgers University. Dr. Schlom directs a translational research program in which the latest advances in immunology and immunotherapy are used to design and develop a range of potential novel immunotherapeutic approaches for a variety of human cancers. His most recent work involves the development of novel therapeutic cancer vaccines, checkpoint inhibitors and immune modulators, both as a monotherapy and in combination therapies. The program focuses on the design and development of novel "off the shelf" immunotherapeutics that can be translated from hypothesis-driven preclinical studies to science-based clinical studies both at the NIH and at numerous Cancer Centers throughout the U.S. Dr. Schlom serves on the editorial boards of numerous scientific journals. He has authored more than 700 scientific publications and holds numerous patents for monoclonal antibody and recombinant vaccine generation and uses.

Position Number of Positions Contact E-mail Contact Name Contact Phone
Postdoctoral Fellow 1

js141c@nih.gov

Jeffrey Schlom, Ph.D. 301-496-4343
Name Position
Lajuan Chase Animal Technician (Contr)
Renee Donahue Ph.D. Postdoctoral Fellow (CRTA)
Benedetto Farsaci M.D. Research Fellow
Romaine I. Fernando Ph.D. Research Fellow
Sofia Gameiro Ph.D. Research Fellow
Bertina Gibbs Animal Technician (Contr)
Italia Grenga M.D. Postdoctoral Fellow (Visiting)
Duane H. Hamilton Ph.D. Research Fellow
Peter Sungwhan Kim Ph.D. Postdoctoral Fellow (CRTA)
Lauren Lepone Ph.D. Postdoctoral Fellow (CRTA)
Diane J. Poole Biological Laboratory Technician
Curits Randolph Animal Technician (Contr)
Jacob Richards Ph.D. Postdoctoral Fellow (CRTA)

Summary

As Chief of the Laboratory of Tumor Immunology and Biology, Dr. Schlom directs a translational research program in cancer immunotherapy. He has pioneered the use of novel immunotherapeutics, both as monotherapy and in combination therapies, for a range of human cancers. His studies involve the translation of hypothesis-driven preclinical studies to science-driven clinical trials. Dr. Schlom’s studies involve the design and development of novel therapeutic cancer vaccines, immunocytokines, and checkpoint inhibitor monoclonal antibodies.

Areas of Expertise
1) immunotherapy 2) vaccines 3) checkpoint inhibitors 4) cancer immunology 5) carcinoma therapy

Research

The Laboratory of Tumor Immunology and Biology (LTIB), CCR, is a multidisciplinary and interdisciplinary translational research programmatic effort with the goal of developing novel immunotherapies for cancer. Within this effort are several research groups, a clinical trials group, two independent tenure track investigators, and multiple collaborations with intramural and extramural scientific and clinical investigators, and with investigators in the private sector. The program takes advantage of the uniqueness of the NCI intramural program in that it spans high-risk basic discovery research in immunology, through preclinical translational research, to paradigm-shifting clinical trials. Focus is placed on the design and development of novel 'off-the-shelf' recombinant vaccines 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. The LTIB strategic plan focuses on the development of novel immunotherapeutics for human carcinomas, 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.

Specifically, my research goals consist of four highly integrated projects:

  1. The design and development of novel immunotherapeutics consisting of recombinant vector-based vaccines and novel immunomodulators such as checkpoint inhibitors and immunocytokines. This is accomplished in collaboration with Cooperative Research and Development Agreements (CRADA) partners in the private sector that provide agents for preclinical studies in appropriate animal models that we have developed, and in our preclinical human in vitro systems. These studies in turn provide the rationale for science-driven clinical studies.
     
  2. The effect of 'non-immune'‒based therapies on the immune system. Emphasis is placed on the analyses of samples from patients treated with these 'non-immune'‒based therapies. These combined studies provide the scientific rationale for combination clinical trials of immunotherapeutics with standard-of-care therapies or other experimental therapies.
     
  3. Clinical studies of the developed immunotherapeutics as monotherapies or as part of an immuno-oncology platform. Principal Investigators (PIs) and Associate PIs on these trials are Drs. J. Gulley, R. Madan (Genitourinary Malignancies Branch, CCR) and C. Heery, who work closely with me and other LTIB members as a well-integrated immunotherapy team. The 'off-the-shelf' immunotherapeutics that we have developed have also enabled collaborations with clinical investigators at extramural Cancer Centers.
     
  4. The analyses of patients' immune responses post- vs. pre-therapy to identify immune correlates of clinical benefit, and/or to identify those patients most likely to benefit from immunotherapy.

SCIENTIFIC OVERVIEW

Recent Accomplishments/Ongoing Studies

  • We have continued our preclinical and clinical investigations of two diverse recombinant (rec.) vaccine platforms: (a) rec. poxviral vectors employing a rec. vaccinia prime followed by multiple rec. fowlpox booster vaccinations; each vector contains the transgenes for one or more tumor-associated antigens (TAAs) and three T-cell costimulatory molecules (designated  TRICOM); and (b) heat-killed rec. Saccharomyces cerevisiae (yeast) containing TAA protein via the insertion of a yeast plasmid.
  • We have further interrogated the transcription factor brachyury, which is a major driver of the epithelial-to-mesenchymal transition (EMT) process in human carcinoma cells, as a novel vaccine target. These studies were conducted in collaboration with Dr. Palena. A rec. yeast-brachyury vaccine has been developed and a first-in-human clinical trial is underway. A Phase II trial in chordoma patients is planned.
  • The C-terminus of MUC1 (MUC1-C) has been shown by others to be an oncogene and is associated with drug resistance and poor prognosis for a range of human tumors. We have now identified 9 novel CD8 T-cell epitopes of MUC1; most importantly, 7 are in the C-terminus. We have identified and characterized enhancer agonist epitopes for each of the 9 epitopes. A rec. yeast-MUC1(agonist) vector has been developed that efficiently processes the agonist epitopes for T-cell activation.
  • In collaboration with our CRADA partner, we have developed a tumor-targeting immunocytokine. NHS-IL12 is a fully human monoclonal antibody (MAb) that is fused to human IL-12. The agent was designed to reduce the toxicity of rec. IL-12 protein while maintaining its immuno-enhancing properties at the tumor site. We have shown that the immunocytokine has anti-tumor activity in a range of tumor models. We have ongoing the first-in-human clinical trial with NHS-IL12.
  • We have developed, in collaboration with our CRADA partner, an anti-PDL1 MAb that, unlike other anti-PDL1 MAbs, is capable of mediating antibody dependent cell-mediated cytotoxicity (ADCC) of human carcinomas cells. We have initiated a first-in-human clinical trial with this anti-PDL1.
  • We have analyzed over 100 immune cell subsets of peripheral blood mononuclear cells (PBMCs) from cancer patients both prior to and during standard-of-care therapies to determine whether specific regimens are suitable for use in combination with immunotherapeutics.

Clinical oncologists Drs. Gulley, Madan (Genitourinary Malignancies Branch, CCR) and Heery (LTIB) along with clinical fellows work closely with scientists of the LTIB in a well-integrated immunotherapy team.

  • Prior Phase II studies with rV-, rF-PSA-TRICOM (PROSTVAC) vaccine as a monotherapy in patients with metastatic castration-resistant prostate cancer (mCRPC) have led to an ongoing Phase III study. This is a global 3-arm study in patients (n=1,200) with asymptomatic mCRPC who receive (a) PROSTVAC, (b) PROSTVAC + GM-CSF, (c) placebo (empty vector). Accrual is complete. The endpoint is overall survival (OS).
  • In collaboration with Dr. A. Fojo at the CCR, we have evaluated the growth rates of tumors (via serum prostate-specific antigen (PSA)) in patients with mCRPC receiving PROSTVAC vaccine or several different chemotherapy regimens. These studies have revealed that, unlike chemotherapy, vaccine therapy can reduce the tumor growth rate leading to enhanced survival even in the absence of increases in progression-free survival (PFS).
  • We have now completed a safety and feasibility study of combined i.t./s.c. PROSTVAC vaccination in men with locally recurrent or progressive prostate cancer. 19/21 patients developed stable or improved PSA levels.
  • Following LTIB preclinical studies, we have completed a Phase I trial in patients with mCRPC of PROSTVAC vaccination with increasing doses of ipilimumab (anti-CTLA4). The OS of patients was quite favorable compared with a similar mCRPC population receiving PROSTVAC alone in a separate trial. These findings provide evidence for the use of vaccine in combination with checkpoint inhibitors such as anti-PDL1.
  • Two randomized studies have recently been completed employing PROSTVAC with standard-of-care therapies. Patients with non-metastatic CRPC received the testosterone-suppressing agent flutamide ± PROSTVAC. This study provided the rationale for the ongoing trials with enzalutamide plus vaccine (see below). In a second recently accrued trial, patients with mCRPC with bone metastases were randomized to receive the bone-seeking radionuclide Quadramet (Sm-153) ± PROSTVAC.
  • A dual center (NCI and MD Anderson) study that randomized patients with metastatic breast cancer to docetaxel ± PANVAC vaccine (rV-, rF-CEA-MUC1-TRICOM) has recently been completed.
  • We have completed a first-in-human Phase I study of rec. yeast-CEA vaccine in patients with metastatic disease and demonstrated safety to the generation of CEA-specific T-cell responses. This has led to the initiation of a Phase II study in patients with metastatic medullary thyroid cancer.
  • Two randomized clinical studies have been initiated employing the novel FDA-approved androgen blockade agent enzalutamide ± PROSTVAC vaccine. The first is in mCRPC patients with a time-to-progression (TTP) endpoint; the second trial is in non-metastatic patients with rising PSA where changes in PSA velocity at the discontinuation of enzalutamide will be evaluated.
  • A clinical study is ongoing in collaboration with Dr. P. Agarwal in the CCR Urologic Oncology Branch (UOB). BCG failure bladder cancer patients will be randomized to second-line BCG ± PANVAC vaccine. The primary endpoint will be tumor extent and immune infiltrate in pre- vs. post-treatment biopsies.
  • Numerous immune analyses pre- vs. post-treatment have been/are being employed in clinical studies in an attempt to identify which patients would most likely benefit from a given immunotherapy, and to evaluate potential immune correlates of clinical benefit early in the treatment cycle.
  • We have now developed a FACS-based assay using 15-mer peptides reflecting entire TAA gene to simultaneously measure both CD4 and CD8 responses; this assay is not restricted by HLA allele. When sufficient PBMCs were available, we have analyzed the number, phenotype and suppressive function of Tregs and function of natural killer (NK) cells post- vs. pre-vaccination.
  • We have analyzed post- vs. pre-serum samples for a range of cytokines as well as two potential immunomodulatory molecules. We have shown that soluble CD40L (sCD40L) is elevated in the sera of patients with prostate cancer and metastatic breast and lung cancers. In vitro studies demonstrated sCD40L could enrich MDSC and expand Tregs. We also have shown that soluble CD27 (sCD27) sera levels are decreased in carcinoma patients vs. healthy donors. In vitro studies demonstrated that sCD27 provides strong proliferative signals to lymphocytes.
  • We have used the multi-color FACS-based assay to define a “peripheral immunoscore” monitoring immune cell subsets known in the literature to have specific immune stimulatory or regulatory functions.
  • We have established a collaboration with Epic Sciences, which has a proprietary method to analyze multiple markers in circulating tumor cells (CTC) in a fixed cytologic platform. This will be especially important in analyzing changes in the expression of brachyury, and mesenchymal and epithelial markers in the same CTCs post- vs. pre-therapy.

ADMINISTRATIVE OVERVIEW

I am involved in the training of numerous postdoctoral and clinical fellows, and medical, college and high school students. I take mentoring very seriously, with frequent meetings with postdoctoral and clinical fellows and with Group Heads. Frequent meetings are held to plan experiments, review and discuss data, and to discuss future plans. Meetings are also held to discuss the preparation of oral presentations, poster presentations, and the writing of manuscripts. All laboratory members attend more formal weekly lab meetings in which planned and ongoing research is discussed. There are also invited seminar speakers, and attendance at the numerous seminars ongoing at the NIH is encouraged.

PROTOCOLS IN PROGRESS AT THE NIH CLINICAL CENTER EMPLOYING LTIB AGENTS AND/OR LTIB IMMUNE MONITORING

  • A randomized, double-blind, phase III efficacy trial of PROSTVAC-V/F ±   GM-CSF in men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer
  • A randomized phase II trial combining vaccine therapy with PROSTVAC / TRICOM and flutamide vs. flutamide alone in men with androgen insensitive non-metastatic (D0.5) prostate cancer
  • A randomized phase II trial combining vaccine therapy with PROSTVAC / TRICOM and enzalutamide vs. enzalutamide alone in men with metastatic castration-resistant prostate cancer
  • A phase II trial of enzalutamide in combination with PSA-TRICOM in patients with non-metastatic castration-sensitive prostate cancer
  • A randomized phase II study of L-BLP25 in combination with standard androgen deprivation therapy and radiation therapy for newly diagnosed high-risk prostate cancer patients
  • A pilot study of recombinant yeast-CEA vaccine in patients with recurrent medullary thyroid cancer
  • First-in-human phase I trial of NHS-IL12 in subjects with metastatic solid tumors
  • A randomized prospective phase II study to determine the efficacy of Bacillus Calmette-Guerin (BCG) given in combination with PANVAC versus BCG alone in adults with high grade non-muscle invasive bladder cancer who failed at least 1 induction course of BCG
  • A phase II study of neoadjuvant rFowlpox-PSA (L155)-TRICOM (PROSTVAC-F/TRICOM) in combination with rVaccinia-PSA (L155)-TRICOM (PROSTVAC-V/TRICOM) in men with prostate cancer undergoing treatment with radical prostatectomy
  • An open-label phase I study to evaluate the safety and tolerability of a modified vaccinia Ankara (MVA)–based vaccine modified to express brachyury and T-cell costimulatory molecules (MVA-brachyury-TRICOM)
Scientific Focus Areas:
Cancer Biology, Clinical Research, Immunology, Stem Cell Biology

Publications

Selected Publications
  1. Roselli M, Fernando RI, Guadagni F, Spila A, Alessandroni J, Palmirotta R, Costarelli L, Litzinger M, Hamilton DH, Huang B, Tucker JA, Tsang KY, Schlom J, Palena C.
    Clin Cancer Res. 18: 3868-79, 2012. [ Journal Article ]
  2. Gulley JL, Arlen PM, Madan RA, Tsang KY, Pazdur MP, Skarupa L, Jones JL, Poole DJ, Higgins JP, Hodge JW, Cereda V, Vergati M, Steinberg SM, Halabi S, Jones E, Chen C, Parnes H, Wright JJ, Dahut WL, Schlom J.
    Cancer Immunol. Immunother. 59: 663-74, 2010. [ Journal Article ]
  3. Gulley JL, Madan RA, Tsang KY, Jochems C, Marte JL, Farsaci B, Tucker JA, Hodge JW, Liewehr DJ, Steinberg SM, Heery CR, Schlom J.
    Cancer Immunol. Res. 2: 133-141, 2013. [ Journal Article ]
  4. Jochems C, Tucker JA, Tsang KY, Madan RA, Dahut WL, Liewehr DJ, Steinberg SM, Gulley JL, Schlom J.
    Cancer Immunol. Immunother. 63: 407-18, 2014. [ Journal Article ]
  5. Schlom J.
    J. Natl. Cancer Inst. 104: 599-613, 2012. [ Journal Article ]

Biography

Dr. Jeffrey Schlom is Chief of the Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH. He received his B.S. from the Ohio State University, M.S. from Adelphi University, and Ph.D. from the Waksman Institute at Rutgers University. Dr. Schlom directs a translational research program in which the latest advances in immunology and immunotherapy are used to design and develop a range of potential novel immunotherapeutic approaches for a variety of human cancers. His most recent work involves the development of novel therapeutic cancer vaccines, checkpoint inhibitors and immune modulators, both as a monotherapy and in combination therapies. The program focuses on the design and development of novel "off the shelf" immunotherapeutics that can be translated from hypothesis-driven preclinical studies to science-based clinical studies both at the NIH and at numerous Cancer Centers throughout the U.S. Dr. Schlom serves on the editorial boards of numerous scientific journals. He has authored more than 700 scientific publications and holds numerous patents for monoclonal antibody and recombinant vaccine generation and uses.

Positions

Position Number of Positions Contact E-mail Contact Name Contact Phone
Postdoctoral Fellow 1

js141c@nih.gov

Jeffrey Schlom, Ph.D. 301-496-4343

Team

Name Position
Lajuan Chase Animal Technician (Contr)
Renee Donahue Ph.D. Postdoctoral Fellow (CRTA)
Benedetto Farsaci M.D. Research Fellow
Romaine I. Fernando Ph.D. Research Fellow
Sofia Gameiro Ph.D. Research Fellow
Bertina Gibbs Animal Technician (Contr)
Italia Grenga M.D. Postdoctoral Fellow (Visiting)
Duane H. Hamilton Ph.D. Research Fellow
Peter Sungwhan Kim Ph.D. Postdoctoral Fellow (CRTA)
Lauren Lepone Ph.D. Postdoctoral Fellow (CRTA)
Diane J. Poole Biological Laboratory Technician
Curits Randolph Animal Technician (Contr)
Jacob Richards Ph.D. Postdoctoral Fellow (CRTA)