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 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. 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 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 (rec.) 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. This is accomplished via Cooperative Research and Development Agreements (CRADAs) with partners in the private sector that provide agents for preclinical studies in appropriate animal models that we have developed and in human in vitro systems. The immunotherapeutics that we have developed have also enabled collaborations with other clinical investigators at extramural Cancer Centers.

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.

Recombinant Vaccine Group:  Dr. James Hodge (Tenure-Track Investigator, Group 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.

Immunoregulation Group:  Dr. Claudia Palena (Tenure-Track Investigator, Group 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.

Translational Research Program:  Dr. Schlom directs the LTIB's translational research program which consists of 4 research groups and a clinical trials group.

  • 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. Kwong Yok Tsang (Senior Associate 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. Benedetto Farsaci (Research Fellow, 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. Jeffrey Schlom (Senior Investigator, Group Head). This group focuses on the design and development of novel cancer immunotherapeutics such as cancer vaccines, checkpoint inhibitors and other immune modulators for use as monotherapies or in combination with standard-of-care and experimental non-immune-based therapeutics. This is accomplished via collaborative efforts with laboratory and clinical investigators in other NCI Branches/Laboratories, at extramural Cancer Centers, and in the private sector.
     
  • Clinical Trials Group:  Dr. Christopher Heery (Staff Clinician, Group Director). This group designs and conducts science-driven clinical studies as a consequence of hypothesis-driven preclinical studies in the laboratory. Dr. Heery works closely with Drs. James Gulley and Ravi Madan (Genitourinary Malignancies Branch), both of whom are Adjunct Investigators in the LTIB, 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.

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)
Position Contact Name Contact E-mail Contact Phone Research Area Keywords Number of Positions
Postdoctoral Fellow Jeffrey Schlom, Ph.D.

js141c@nih.gov

301-496-4343

Immunology, immunotherapy, vaccines

1

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 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. 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 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 (rec.) 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. This is accomplished via Cooperative Research and Development Agreements (CRADAs) with partners in the private sector that provide agents for preclinical studies in appropriate animal models that we have developed and in human in vitro systems. The immunotherapeutics that we have developed have also enabled collaborations with other clinical investigators at extramural Cancer Centers.

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.

Recombinant Vaccine Group:  Dr. James Hodge (Tenure-Track Investigator, Group 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.

Immunoregulation Group:  Dr. Claudia Palena (Tenure-Track Investigator, Group 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.

Translational Research Program:  Dr. Schlom directs the LTIB's translational research program which consists of 4 research groups and a clinical trials group.

  • 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. Kwong Yok Tsang (Senior Associate 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. Benedetto Farsaci (Research Fellow, 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. Jeffrey Schlom (Senior Investigator, Group Head). This group focuses on the design and development of novel cancer immunotherapeutics such as cancer vaccines, checkpoint inhibitors and other immune modulators for use as monotherapies or in combination with standard-of-care and experimental non-immune-based therapeutics. This is accomplished via collaborative efforts with laboratory and clinical investigators in other NCI Branches/Laboratories, at extramural Cancer Centers, and in the private sector.
     
  • Clinical Trials Group:  Dr. Christopher Heery (Staff Clinician, Group Director). This group designs and conducts science-driven clinical studies as a consequence of hypothesis-driven preclinical studies in the laboratory. Dr. Heery works closely with Drs. James Gulley and Ravi Madan (Genitourinary Malignancies Branch), both of whom are Adjunct Investigators in the LTIB, 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.

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)

Clinical Trials

PI & Key Staff

Positions

Position Contact Name Contact E-mail Contact Phone Research Area Keywords Number of Positions
Postdoctoral Fellow Jeffrey Schlom, Ph.D.

js141c@nih.gov

301-496-4343

Immunology, immunotherapy, vaccines

1

Contact Info

Laboratory of Tumor Immunology and Biology
Center for Cancer Research
National Cancer Institute
Building 10, Room 8B09
Bethesda, MD 20892-1750
301-496-4343