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Robust Partnerships Aid Development Of Cancer Vaccines

Private companies may have great technology, but they often need an academic environment to apply it. Dr. Gilda Hillman's lab serves in that capacity for Antigen Express, Transgene and Chiron - all of whom are interested in developing cancer vaccines.

During the past decade, Dr. Gilda Hillman has developed animal tumor models for prostate carcinoma and renal-cell carcinoma. These models involved implantation of tumor cells in the prostate, bones or kidneys of mice, which leads to development of cancer that mimics the progression of prostate or kidney cancer in humans. Using these tumor models, Dr. Hillman has developed therapeutic approaches based on the combination of local tumor irradiation and immunotherapy with cytokines. Cytokines are growth factors used to activate and enhance immune responses directed against cancer cells. Their effect on metastatic disease is enhanced by radiation of the primary tumor.

Dr. Hillman is collaborating with Antigen Express Inc. to add a cancer vaccine to her combinedmodality approach to induce a longlasting immune response, specific to the cancer cells. The cancer vaccine approach developed by Antigen Express is to genetically modify cancer cells to cause induction of MHC Class II molecules and suppression of the Invariant Chain (Ii) immunoregulatory protein. This inhibits the binding of antigens to Class II molecules and therefore interferes with stimulation of helper T immune cells needed to trigger cell-mediated immune response against cancer cells. Antigen Express developed oligonucleotides that help transform tumor cells into potent stimulators of immune response, or potential cancer vaccines.

“By bringing together Wayne State University and Antigen Express, we have developed a mechanism for testing the potency of the novel cancer vaccine approach in preclinical animal models,” said Dr. Hillman. “We have developed an intense collaboration that is proving to be fruitful for both sides. The company has great abilities in technology, but they need an academic environment to apply that technology.”

Earlier this year, Antigen Express received a $192,000 Small Business Innovative Research (SBIR) grant from the National Institutes of Health to support this research for prostate cancer with Dr. Hillman as the academic collaborating investigator.

Other companies that have made solid commitments to Wayne State’s cancer vaccine, gene therapy and immunotherapy research are Transgene and the Chiron Corp. Transgene provides Dr. Hillman with adenovectors containing interleukin-2 (IL-2) and funding for her work in animal models. In turn, Dr. Hillman helped them establish a renal cell carcinoma mouse model. Chiron, which already markets IL-2 for renal cancer, provides IL-2 free of charge for Dr. Hillman’s experimental prostate cancer studies, hoping it will be also effective for this disease.

Dr. Hillman’s benchwork has already crossed to translational research, through clinical trials with Drs. Jeffrey Forman and Malcolm Mitchell that are investigating new cancer treatments that combine radiation to the primary tumor and systemic immunotherapy with IL-2.

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Bibliographies:
Anatomy and Cell Biology

Barbara Ann Karmanos Cancer Institute

Biochemistry and Molecular Biology

Center for Healthcare Effectiveness Research