Over the past year, we have researched an immunotherapeutic strategy that employs recombinant and synthetic forms of tumor associated antigens (TAA) that are recognized by immune cells. This approach is possible because TAA have now been cloned. As a result, instead of using tumor cells as immunogens, we have utilized synthetic peptides whose sequences correspond to epitopes of TAA that are recognized by T lymphocytes. We have also inserted genes encoding TAA into recombinant vectors. We have attempted to use these immunogens in the treatment of established cancer. Our most important immunological finding is that mice bearing model-Ag expressing tumors can be treated successfully when they are inoculated with viruses capable of mediating the expression of the same model antigens. Such an experimental result has clear implications for the design of new immunotherapeutic strategies in the clinic. We have found immunomodulatory molecules that can enhance the ability of recombinant and synthetic immunogens to mediate the regression of an established tumor. In particular, the administration of the T lymphocyte growth and differentiation factors IL-2, IL-12, IL-10 and B7-1 have profound adjuvant activity. We continue to improve the function of recombinant anti-cancer vaccines in the laboratory, and we are translating these findings into clinical trials.
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