EDWARD P. COHEN
epcohen@uic.edu
312-996-9479
Professor
MD, Washington University (St. Louis)
Cancer Therapy with DNA Vaccines
My laboratory is engaged in preclinical models for the development of vaccines that can induce anti tumor immune responses in cancer patients. The approach we take is based on two seminal findings. The first is that tumor associated antigens expressed by neoplastic cells are the products of mutant or dysregulated genes in cancer cells. The products of these genes differ from the products of the homologous genes in normal, non-neoplastic cells of the tumor-bearing host. Under appropriate circumstances, antigens associated with malignant cell scan become the "targets" of immune-mediated attack. The second is that transfection of genomic DNA from one cell type can stably modify the genotype of the recipient cells. The transferred DNA is integrated and donor genes can be expressed by the recipient cells. Tumor antigennegative cells, for example, can be converted to cells that express tumor antigens by transfection of genomic DNA from cancer cells.
We combine these two concepts to develop a tumor vaccine. We transfer DNA from neoplastic cells into a highly immunogenic cell line. The transfected cells express tumor antigens in ahighly immunogenic form as indicated by the finding that experimental animals immunized with the DNA tranfected cells developed strong immune responsess. They were specific for the type of tumor cell from which the DNA was obtained. In addition to the relevance of this approach in the treatment of cancer patients, transfer of DNA from cancer cells into an immunogenic cell line provides an opportunity to investigate fundamental questions relating to the interaction of cancer cells with the host, the identification and characterization of genes specifying tumor antigens and mechanisms used by cancer cells to escape immune defenses.
Kim, T.S. and E.P. Cohen. 1994. Interleukin-2-secreting mouse fibroblasts transfected with genomic DNA from murine melanoma cells prolong the survival of mice with melanoma. Cancer Research, 54 (May): 2531-2535.
Kim, T.S., W. S. Xu, E. de Zoeten, and E.P. Cohen. Immunization with interleukin-2/interferon-g double cytokine-secreting allogeneic fibroblasts prolong the survival of mice with melanoma. Melanoma Research, 5: 217-227, 1995.
Sun, T., T.S. Kim, M.R. Waltz and E.P. Cohen Interleukin-2 secreting mouse fibroblasts transfected with genomic DNA from murine neoplasms induce tumor-specific immune responses that prolong the lives of tumor-bearing mice. Cancer Gene Therapy, 2: 183-190, 1995.
Sun, T., de Zoeten, E., Carr-Drendel, V., and Cohen, E.P. Immunization with interleuken-2-secreting allogenic sells transfected with DNA from mouse melanoma cells induces immune responses that prolong the lives of mice with melanoma., Cancer Gene Therapy, 5: 110-118, 1998.
Xu, W., de Zoeten, E. F., Carr-Brendel, V. and Cohen, E.P. Co-expression of immunogenic determinants by the same cellular immunogen is required for an optimum immunotherapeutic benefit in mice with melanoma. Cancer Immunology Immunotherapy, 45: 217-224, 1998.
de Zoeten, E.F., Carr-Brendel, V. and Cohen, E.P. Resistance to melanoma in mice immunized with semi-allogeneic fibroblasts transfected with genomic DNA from melanoma cells. Journal of Immunology, 160: 2915-2822, 1998.
de Zoeten, E., Carr-Brendel, V., Markovic, D., Taylor-Papadimitriou and Cohen. E.P. Immunity to Breast Cancer in Mice Immunized with Semi-Allogeneic Fibroblasts Transfected with DNA from Breast Cancer Cells. Journal of Immunology, 162: 6934-6941,1999
Cohen, E.P., de Zoeten, E.F. and Schatzman, M. DNA-vaccines for the treatment of cancer. American Scientist 87:328-335, 1999.
Other Publications