James W. Hodge, Ph.D., M.B.A.
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.
1) immunotherapy, 2) cancer vaccines, 3) radiation, 4) chemotherapy,
5) combination therapies, 6) cytotoxic T-cells (CTL)
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.
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
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 ]
Tumor cells surviving exposure to proton or photon radiation share a common immunogenic modulation signature, rendering them more sensitive to T cell-mediated killing.Int J Radiat Oncol Biol Phys. 95(1): 120-30, 2016. [ Journal Article ]
Androgen deprivation therapy sensitizes prostate cancer cells to T-cell killing through androgen receptor dependent modulation of the apoptotic pathway.Oncotarget. 2(19): 9335-48, 2014. [ Journal Article ]
Immune consequences of decreasing tumor vasculature with antiangiogenic tyrosine kinase inhibitors in combination with therapeutic vaccines.Cancer Immunol Res. 2(11): 1090-1102, 2014. [ Journal Article ]
A potential therapy for chordoma via antibody-dependent cell-mediated cytotoxicity employing NK or high-affinity NK cells in combination with cetuximab.J Neurosurg. 128(5): 1419-27, 2018. [ Journal Article ]
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. He was awarded tenure in 2016. 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.
|Kellsye Fabian Ph.D.||Research Fellow|
|Elizabeth Franks Ph.D.||Postdoctoral Fellow (CRTA)|
|Benjamin R. Wolfson Ph.D.||Postdoctoral Fellow (CRTA)|