Bacille Calmette-Guerin (BCG) is becoming the treatment of choice for superficial bladder tumors. Prospective randomized clinical trials have shown that the efficacy of intravesical BCG as an adjuvant to surgery is superior to surgery alone or adjuvant chemotherapy. The mechanisms by which BCG mediates antitumor activity are not well understood. Data from clinical trials on bladder cancer patients as well as studies on animal tumor models suggest that BCG-mediated modulation of immune responsiveness is closely associated with efficacy; however, the active components remain an enigma. A better understanding of the mechanisms of action of BCG may lead to the developement of prognostic indicators and more effective therapeutic regimens. To this end a mouse bladder tumor model in which tumors are implanted directly into bladders has been adapted for the study of intravesical BCG therapy. Using this model, recent developments in monoclonal antibodies to cell surface differentiation antigens, flow cytometry techniques and immunomodulatory techniques will be utilized to determine BCG-mediated antitumor mechanisms. During BCG therapy, the responding lymphoid cells in the bladder, regional lymph nodes and spleens will be identified by flow cytometry analysis of appropriately labelled cells. These cells will then be isolated and functional capacities will be determined. The same process will be repeated with animals compromised immunologically by alteration of T cells, macrophage or natural killer cell responsiveness. Adoptive transfer of specific lymphoid subpopulations will be performed to verify the role of lymphoid cells in BCG-mediated antitumor activity.
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