EVOLUTION AND CLINICAL-SIGNIFICANCE OF THE T-CELL PROLIFERATIVE AND CYTOKINE RESPONSE DIRECTED AGAINST THE FIBRONECTIN-BINDING ANTIGEN-85 COMPLEX OF BACILLUS-CALMETTE-GUERIN DURING INTRAVESICAL TREATMENT OF SUPERFICIAL BLADDER-CANCER

Purpose: The antitumorigenic effect of intravesical bacillus Calmette- Guerin (BCG) in superficial bladder cancer was reported to be initiate d by the attachment of BCG to the bladder wall via fibronectin. The an tigen 85 complex secreted in BCG culture filtrate binds specifically t o fibronectin and is a powerful T cell stimulus. Therefore, we investi gated the evolution and clinical significance of the cellular prolifer ative response and cytokine production during intravesical BCG therapy against this purified antigen 85 complex. Materials and Methods: Evol ution of the lymphoproliferation, interleukin-2 and interferon-gamma p roduction of peripheral blood lymphocytes against tuberculin (purified protein derivative), purified antigen 85, BCG culture filtrate, whole BCG bacilli and pokeweed mitogen was tested before and after 6 weekly intravesical BCG instillations in 29 patients with superficial bladde r cancer at intermediate or high risk for recurrence. Results: A major increase in the lymphoproliferative response against purified protein derivative, antigen 85, BCG culture filtrate, whole BCG and pokeweed mitogen was observed in 69.0, 65.5, 79.3, 48.3 and 65.3% of the patien ts, respectively, analyzed after BCG therapy. Reactivity returned to b aseline values at 6 months of followup. Of the patients who received a second BCG course because of tumor recurrence 66% had a novel increas e in lymphoproliferation against antigen 85. An increase in the produc tion of interleukin-2 and interferon-gamma by peripheral lymphocytes a gainst antigen 85 was noted in 42.1 and 50% of the treated patients, r espectively, after a single BCG course. During a mean followup of 23.1 1 months 48.5% of the patients remained tumor-free. No correlation cou ld be found between the immunological response against any of the BCG antigens and the clinical evolution of the response. Conclusions: Intr avesical BCG instillations induce a transient (less than 6 months) per ipheral immune activation against several purified BCG antigens and am ong them the fibronectin binding antigen 85 complex. Reactivation is o bserved in most cases after additional BCG courses. The absence of lon g lasting immune activation after a single 6-week course of BCG could be related to the increased clinical efficacy observed with BCG mainte nance instillations.