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Jeffrey  Schlom, Ph.D.

Jeffrey Schlom, Ph.D.

  • Center for Cancer Research
  • National Cancer Institute
  • Building 10, Room 8B09
  • Bethesda, MD 20892-1750
  • 240-858-3463
  • js141c@nih.gov

RESEARCH SUMMARY

As Co-Director of the Center for Immuno-Oncology, Dr. Schlom directs a translational research program in cancer immunology and 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 works closely with clinicians in the CIO and with investigators in multiple Laboratories/Branches of the NCI and NIH, and at extramural Cancer Centers. Dr. Schlom also works closely with investigators in multiple Biotech and Pharma companies, via Cooperative Research and Development Agreements, to rapidly translate preclinical findings into agents for clinical studies. Dr. Schlom’s studies involve the design and development of novel therapeutic cancer vaccines, immunocytokines, checkpoint inhibitor monoclonal antibodies, inhibitors of immune suppressive entities, as well as agents and strategies to modify the tumor microenvironment to render tumor cells more susceptible to immune-mediated therapy.

Areas of Expertise

Vaccines
Checkpoint Inhibitors
Immune Modulation

Publications

Selected Recent Publications

Tumor-targeted interleukin-12 synergizes with entinostat to overcome PD-1/PD-L1 blockade-resistant tumors harboring MHC-I and APM deficiencies

Minnar CM, Chariou PL, Horn LA, Hicks KC, Palena C, Gameiro SR, Schlom J
J ImmunoTher Cancer. 10(6): e004561, 2022.
Full-Text Article
[ Journal Article ]

An interleukin-15 superagonist enables antitumor efficacy of natural killer cells against all molecular variants of SCLC

Fousek K, Horn LA, Qin H, Dahut M, Iida M, Yacubovich D, Hamilton DH, Thomas A, Schlom J, Palena C
J Thorac Oncol. 18(3): 350-368, 2023.
Full-Text Article
[ Journal Article ]

Tumour-targeted interleukin-12 and entinostat combination therapy improves cancer survival by reprogramming the tumour immune cell landscape

Hicks KC, Chariou P, Ozawa Y, Minnar C, Knudson KM, Meyer T, Bian J, Cam M, Gameiro SR, Schlom J.
Nat Commun. . 12(1):5151: 5151, 2021.
Full-Text Article
[ Journal Article ]

Immune correlates of clinical parameters in patients with HPV-associated malignancies treated with bintrafusp alfa

Tsai Y-T, Strauss J, Toney NJ, Jochems C, Gulley JL, Donahue RN, Schlom J.
J ImmunoTher Cancer . 10(4): e004601, 2022.
Full-Text Article
[ Journal Article ]

Bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with human papillomavirus-associated malignancies

Strauss J, Gatti-Mays M, Cho BC, Hil A, Salas S, McClay E, Redman J, Abdul Sater H, Donahue R, Jochems C, Lamping E, Burmeister A, Marté J, Cordes L, Bilusic M, Karzai F, Ojalvo L, Jehl G, Rolfe PA, Hinrichs CS, Madan R, Schlom J, Gulley JL
J ImmunoTher Cancer. 8(2): e001395, 2020.
Full-Text Article
[ Journal Article ]

Job Vacancies

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Team

Lajuan Chase
Animal Technician (Contr.)
Lajuan Chase
Carolina Celades Errando
Postdoctoral Fellow (Visiting Fellow)
Carolina Celades Errando, M.D.
Animal Technician (Contr)
Elmer Contreras
Emily Gonzalez
Animal Technician (Contr)
Emily Gonzalez
Meg Goswami, PhD
Postdoctoral Fellow (CRTA)
Meg Goswami, Ph.D.
Maria Del Mar Gracia Hernandez
Visiting Fellow
Maria Del Mar Gracia Hernandez, Ph.D.
Sarah Khelifa
Postdoctoral Fellow (CRTA)
Sarah Khelifa, Ph.D.
Loc H. Le
Biologist
Loc H. Le, Ph.D.
Katherine E. Lothstein
Postdoctoral Fellow (CRTA)
Katherine E. Lothstein, Ph.D.
Megan Lynch
Bioinformatics Scientist
Megan Lynch, Ph.D.
Maria Del Mar Maldonado Montalban
Postdoctoral Fellow (CRTA)
Maria Del Mar Maldonado Montalban, Ph.D.
Christine M. Minnar
Bioinformatics Scientist
Christine M. Minnar, Ph.D.
Masaya Miyamoto
Special Volunteer
Masaya Miyamoto, Ph.D.
Yvetane E. Moreau
Biologist (Contr)
Yvetane E. Moreau
Dilia Penate-Pacheco
Program Specialist
Dilia Penate-Pacheco
Steffie Pitts
Postdoctoral Fellow (CRTA)
Stephanie C. Pitts, Ph.D.
Lisa K. Poppe
Postdoctoral Fellow (CRTA)
Lisa K. Poppe, Ph.D.
Curtis Randolph
Biological Science Laboratory Technician (Animal)
Curtis Randolph
Robin Riley
Program Manager
Robin Riley
Nicholas T. Roller
Biologist
Nicholas T. Roller
Angela Schwab
Biologist
Angela Schwab
Nicole J. Toney, PhD
Postdoctoral Fellow (CRTA)
Nicole J. Toney, Ph.D.
Yo-Ting Tsai, PhD
Research Fellow
Yo-Ting Tsai, Ph.D.
Debra L. Weingarten
Editor
Debra L. Weingarten
Keanan Wright
Biologist (Contr.)
Keanan Wright

News

Novel T cell stimulation technique drives potent anti-tumor response

STAR0602, a bifunctional therapeutic molecule, selectively activates a subset of T cells through both the TCR and IL-2 receptor signaling pathways. Immunological and antitumor effects in mice were recapitulated in studies of STAR0602 in nonhuman primates and human ex vivo models, wherein STAR0602 boosted human antigen-specific T cell responses and killing of tumor organoids. Thus, STAR0602 represents a distinct class of T cell–activating molecules with the potential to deliver enhanced antitumor activity in checkpoint inhibitor–refractory settings. A phase 1/2 first-in-human, open-label, dose escalation and expansion study of STAR0602 in patients with advanced metastatic cancer has recently commenced. Sci Transl Med. 2023;15(724):eadi0258. doi: 10.1126/scitranslmed.adi0258

https://ccr.cancer.gov/news/article/novel-t-cell-stimulation-technique-drives-potent-anti-tumor-response?cid=eb_govdel&utm_campaign=January+2024&utm_medium=govdelivery&utm_source=Snapshots

Clinical trial researches bone marrow transplants for blood cancers. A clinical trial led by Christopher G. Kanakry, M.D., Lasker Clinical Research Scholar in the Center for Immuno-Oncology, is researching bone marrow transplants [and whether the lymphocytes they contain can help reduce relapse risk] for some types of blood cancers, such as high-risk leukemia, lymphoma, myelodysplastic syndrome or multiple myeloma.

https://ccr.cancer.gov/news/article/clinical-trial-researches-bone-marrow-transplants-for-blood-cancers

 Clinical trial researching therapy for recurrent respiratory papillomatosis. A clinical trial led by Scott M. Norberg, D.O., Assistant Research Physician in the Center for Immuno-Oncology, is leading a trial researching drug therapy that may help reduce necessary surgeries for recurrent respiratory papillomatosis.

https://ccr.cancer.gov/news/article/clinical-trial-researching-therapy-for-recurrent-respiratory-papillomatosis-0

Tumor-targeted interleukin-12 synergizes with entinostat to overcome PD-1/PD-L1 blockade-resistant tumors harboring MHC-I and APM deficiencies. Tumor-intrinsic loss of major histocompatibility complex class I (MHC- I) and aberrations in antigen processing machinery (APM) and interferon gamma (IFN-γ) pathways have been shown to play an important role in immune checkpoint blockade resistance. We demonstrated that the combination of entinostat and NHS- IL12 therapy elicits potent antitumor activity across αPD- 1/αPD- L1 refractory tumors. Our findings provide a rationale for combining the tumor-targeting NHS- IL12 with the histone deacetylase inhibitor entinostat in the clinical setting for patients unresponsive to αPD- 1/αPD- L1 and/or with innate deficiencies in tumor MHC- I, APM expression, and IFN-γ signaling. Minnar et al. Journal for ImmunoTherapy of Cancer 10(6):e004561, 2022.

https://jitc.bmj.com/content/10/6/e004561.long

Tumour-targeted interleukin-12 and entinostat combination therapy improves cancer survival by reprogramming the tumor immune cell landscape. Poorly inflamed carcinomas do not respond well to immune checkpoint blockade. Converting the tumor microenvironment into a functionally inflamed immune hub would extend the clinical benefit of immune therapy to a larger proportion of cancer patients. We have shown that Entinostat, a class I histone deacetylase inhibitor, facilitates accumulation of the necrosis-targeted recombinant murine immune-cytokine, NHS-rmIL12, in  poorly immunogenic tumors. This combination therapy reprograms the tumor innate and adaptive immune milieu to an inflamed landscape. Collectively, these findings provide a rationale for combining NHS-IL12 with Entinostat in the clinical setting. Hicks et al. Nature Communications 12(1):5151; 2021.

https://www.nature.com/articles/s41467-021-25393-x

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

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

Immunotherapy drug with two targets shows promise against HPV-related cancers. In a Phase 1 clinical trial at the NCI of 43 patients with advanced cancers, the investigational immunotherapy drug bintrafusp alfa shrank the tumors of some patients with advanced human papillomavirus (HPV)-related cancers. “This drug is a promising agent for patients with HPV-related cancers and may potentially benefit these patients more than traditional checkpoint therapies,” said the trial's Principal Investigator, Julius Strauss, M.D., Laboratory of Tumor Immunology and Biology, CCR, NCI.

https://www.cancer.gov/news-events/cancer-currents-blog/2019/immunotherapy-y-trap-hpv-cancers

Clinical trial tests immunotherapy combination for advanced HPV-associated cancers. Dr. Julius Strauss is leading a study using a combination of 3 immunotherapy drugs to treat HPV+ cancers. [NCT04287868]

https://ccr.cancer.gov/news/article/clinical-trial-tests-immunotherapy-combination-for-advanced-hpv-associated-cancers

New trial evaluates immunotherapy combinations in adults with advanced small bowel and colorectal cancers is being led by Dr. Julius Strauss. [NCT04491955]

https://ccr.cancer.gov/news/article/new-trial-evaluates-immunotherapy-combinations-in-adults-with-advanced-small-bowel-and-colorectal-cancers

Clinical trial will test triple-drug combination against aggressive colon and HPV-associated cancers. Dr. Julius Strauss discusses promising immunotherapy drug for patients with HPV-related cancers. [NCT04708470]

https://ccr.cancer.gov/news/article/clinical-trial-will-test-triple-drug-combination-against-aggressive-colon-and-hpv-associated-cancers