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Cancer Control Research

Abstract

Current understanding of the complex cellular interactions involved in the immune reaction to tumor-specific antigens illuminates the suppressor system as a potential target for cancer therapy. If suppressive regulation of the tumor-specific immune response could be eliminated specifically, or reduced, the tumor rejection potential of the host would be augmented significantly. The existence of differential biochemical susceptibility among sub-populations of immune cells suggests that the balance between beneficial and detrimental components of the tumor-specific immune response (i.e., immune rejection potential) can be altered favorably through pharmacological means. Therefore, we plan to evaluate a therapeutic strategy for the specific elimination of suppressor activity in the tumor host through pharmacological means. A spontaneous autochthonous murine breast tumor model will be employed to identify drugs (dosages, drug combinations, and treatment schedules) which will result in specific reduction of suppressor activity with no, or minimum, interference with the beneficial components of the tumor-specific immune response. Treatment will be monitored by in vitro assay of non-specific (PHA-stimulation), and tumor-specific immune suppressor activity, as well as by assay of tumor-specific cytotoxic activities including direct cell-mediated cytotoxicity, and antibody mediated, complement-dependent and lymphocyte-dependent, cytotoxicity. Therapeutic efficacy of the various drug treatments will be evaluated in the autochthonous-tumor-bearing host, against a large tumor burden, and against residual local and metastatic tumor foci after reduction of the tumor burden with surgery and/or conventional cancer chemotherapy. The spontaneous, autochthonous murine breast tumor to be employed here is considered to be an excellent model for the human disease, and therefore, it is anticipated that results forthcoming from these studies will provide a basis for translation of a pharmacological approach to immunotherapy of cancer in man.