James W. Hodge, Ph.D., MBA
Dr. Hodge pioneered the development of vaccines and vaccine strategies for cancer immunotherapy including a) recombinant vectors to deliver tumor antigens, b) the use of costimulation to enhance antitumor T-cell responses, c) the combined use of vaccines with radiation, chemotherapy, and targeted small-molecule therapeutics. These concepts and therapeutics have been translated into many randomized multi-center trials at numerous Cancer Centers.
The LTIB strategic plan focuses on the development of novel vaccines 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 immune-oncology programmatic effort.
Overview. My group is involved in the development of novel recombinant vaccines, and vaccine combinatorial therapies. We study both mechanistically and operationally how certain radiation modalities, chemotherapy agents, small molecule targeted therapies, and immune modulators a) alter the tumor to become an immunostimulatory milieu, or b) modulate the tumor microenvironment to create a more immunopermissive hub, to enhance vaccine efficacy. Our team has worked independently and collaboratively with the LTIB on the design, engineering, and development of recombinant poxvirus and yeast-based cancer vaccine platforms. The poxviral vector-based vaccines contain transgenes for tumor antigens and for multiple synergistic costimulatory molecules. Theses TRICOM-based vaccines have led to several clinical trials showing patient survival benefit for a range of human carcinomas, with the PSA-TRICOM vaccine currently in a Phase III clinical trial for metastatic prostate cancer.
Research Focus. Immune consequences of cancer therapy include both direct effects on tumor cells and modulation of the immune system. My laboratory has focused on two areas: immunogenic modulation and immune subset conditioning. Immunogenic modulation describes the mechanism of how anticancer therapies alter the biology of the surviving tumor cells to render them more sensitive to immune mediated killing. Immunogenic modulation encompasses a spectrum of molecular alterations in the biology of the cancer cell that independently or collectively make the tumor more amenable to cytotoxic T lymphocyte (CTL)‒mediated destruction. Immune subset conditioning describes how anticancer therapies mediate the peripheral and/or intratumoral reduction of negative regulatory elements into a more immune-permissive environment for vaccine immunotherapy. Understanding the underlying mechanisms of these areas provide a rationale for the use of immunotherapy in combination with radiation, chemotherapy, small molecule inhibitors, and immune modulators. For a list of publications from the Recombinant Vaccine Group, see Dr. Hodge's Full PubMed Summary.
Selected Key Publications
- Cancer Res. 59: 5800-7, 1999. [ Journal Article ]
Exploitation of differential homeostatic proliferation of T-cell subsets following chemotherapy to enhance the efficacy of vaccine-mediated antitumor responses.Cancer Immunol Immunother. 60: 1227-42, 2011. [ Journal Article ]
Chemotherapy-induced immunogenic modulation of tumor cells enhances killing by cytotoxic T lymphocytes and is distinct from immunogenic cell death.Int. J. Cancer. 133: 624-36, 2013. [ Journal Article ]
Radiation-induced immunogenic modulation of tumor enhances antigen processing and calreticulin exposure, resulting in enhanced T-cell killing.Oncotarget. 5: 403-16, 2014. [ Journal Article ]
Combination therapy with a second-generation androgen receptor antagonist and a metastasis vaccine improves survival in a spontaneous prostate cancer model.Clin. Cancer Res. 19: 6205-18, 2013. [ Journal Article ]
Recombinant Vaccine Group Dr. Hodge is a Senior Investigator and head of the Recombinant Vaccine Group in the Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH, Bethesda, MD. Dr. Hodge received his Ph.D. in Comparative and Experimental Medicine from the University of Tennessee, and his MBA from the George Washington University. Dr. Hodge is active in the area of tumor immunity, and has made significant contributions to the design and development of novel recombinant vaccines and vaccine strategies for cancer immunotherapy including a) recombinant vectors to deliver tumor antigens, b) the use of costimulation to enhance antitumor T-cell responses, c) the combined use of vaccines with radiation, chemotherapy, and targeted small-molecule therapeutics. The concepts and therapeutics developed within the Recombinant Vaccine Group have been translated into many randomized multi-center trials at numerous Cancer Centers.
|Rika Fujii M.D., Ph.D.||Postdoctoral Fellow (Visiting)|
|Sofia Gameiro, Ph.D.||Staff Scientist|
|Kristin C. Hicks Ph.D.||Postdoctoral Fellow (CRTA)|
|Karin M. Knudson Ph.D.||Postdoctoral Fellow (CRTA)|
|Anthony Malamas Ph.D.||Postdoctoral Fellow (CRTA)|
|Michelle Padget||Biologist (Contr)|
|Curtis Randolph||Laboratory Technician (Contr)|
|Marion Taylor||Biological Laboratory Technician|