Surgical adjuvant intravesical bacille Galmette-Guerin (BCG) is considered 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 either surgery alone or intravesical chemotherapy (thiotepa, adriamycin). The mechanisms by which BCG mediates antitumor activity are not well characterized. Animal studies show that an active immune response is required for BCG-mediated antitumor activity. Moreover, data from BCG-treated bladder cancer patients demonstrate that immune responsiveness correlates significantly with effective antitumor therapy; however, an understanding of specific immunomodulating responses induced by intravesical BCG in humans has not been reported. A clear understanding of the immunomodulating effects of BCG may lead to better patient selection, the development of prognostic indicators and more effective therapeutic regimens. Studies are proposed to define the immune responses modulated in patients treated with intravesical BCG. Both the local inflammatory response induced in the bladder and the systemic response will be studied. The cells infiltrating the bladder will be identified using monoclonal antibodies to cell surface antigens. Similar methods will be used to study BCG-induced peripheral blood mononuclear cell modulation. Also, functional studies on local inflammatory and peripheral blood cells will be performed including: (a) presence or absence of specific responses to mycobacterial and tumor associated antigens, (b) antigen presenting capacity of appropriate cells, (c) suppressor cell activity, and (d) nonspecific cell-mediated killer cell activity.
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