176 Vector-based Vaccines for Cancer Therapy

Abstract

Our program has been involved in the design and development of recombinant vector based vaccines for the therapy of human carcinomas. Emphasis has been based on the development of a pox virus-based regimen, i.e., recombinant vaccinia prime vaccination followed by multiple booster vaccinations with recombinant fowlpox vectors. Clinical trials have demonstrated that one can administer multiple boosts of recombinant fowlpox without host neutralizing activity. Vaccines have now been developed which contain transgenes for three human T-cell costimulatory molecules (TRICOM) and transgenes for either PSA for prostate cancer vaccines, or CEA-MUC-1 for use in the therapy of most carcinomas. These vaccines have demonstrated evidence of antigen-specific T-cell responses, the initiation of antigen cascade, objective clinical responses, drops in serum markers, delays in time to progression, and most importantly, evidence of increase in patient survival. In two separate clinical trials, evidence of increased survival has been observed in prostate cancer patients with hormone refractory disease and with metastatic disease, respectively. Preclinical studies have clearly demonstrated that vaccine-induced T-cell immunity can act synergistically with radiation therapy, and certain chemotherapeutic agents by altering the phenotype of tumor cells to make them more susceptible to T-cell-mediated attack. Evidence is also emerging that the dynamic process of T-cell-mediated immunity initiated by vaccine therapy can have a positive influence on subsequent therapies.