Surgically incurable melanoma is a devastating disease with a median survival of only 9-12 months despite the best available chemotherapy. Recent studies employing active immunotherapy approaches for melanoma have begun to yield encouraging results. Despite this, our understanding of human immune response subsequent to immunological intervention is, at present quite limited. Thus the need to fully exploit patient material obtained from clinical trials of such therapy is apparent. An enhanced understanding of host immune responses is crucial to the rational design of future therapies. The applicant has undertaken two clinical trials which attempt to augment host antitumor immune responses through the administration of recombinant canary pox viruses encoding the cytokine, human IL-12 (ALVAC-hIL-12) or the human costimulatory molecule, B7.1 (ALVAC-hB7.1), separately and in combination. Here she proposes to use the patient material generated in these two immunotherapy trials for two purposes. First, she will characterize patient T cell responses elicited in response to these cancer vaccines by evaluating peripheral blood and tumor infiltrating lymphocytes for cytolytic T cell activity and cytokine release in response to known tumor antigens. A second goal is to use patient tumor and sera samples to identify and characterize cryptic tumor-associated antigens employing a serologically based method of tumor antigen identification (SEREX). She anticipates that these studies will advance our understanding of the interaction between cancer and the immune system, and identify novel targets for immunotherapy, thereby facilitating the development of improved cancer vaccines. Characterization of the cellular immune response to previously characterized melanoma-associated antigens will also provide data critical in making the decision as to whether these novel vaccine strategies should be pursued in subsequent Phase II trials.
