Serum TA90 antigen-antibody complex as a surrogate marker for the efficacyof a polyvalent allogeneic whole-cell vaccine (CancerVax) in melanoma

Introduction: TA90 is a tumor-associated 90-kD glycoprotein antigen express ed on most melanoma cells, including those of CancerVax, a polyvalent allog eneic whole-cell vaccine. Previous studies have shown that a TA90 antigen-a ntibody immune complex (IC) in the serum of patients with melanoma is a mar ker of subclinical tumor burden and a strong prognostic factor. We hypothes ized that the induction of TA90-IC during postoperative adjuvant CancerVax therapy might indicate vaccine-mediated immune destruction of subclinical m elanoma cells with release of TA90, and thereby serve as a surrogate marker of vaccine efficacy. Methods: From 1993 to 1997, 219 melanoma patients were enrolled in a prospe ctive phase II trial of CancerVax plus bacille Calmette-Guerin (BCG) after complete tumor resection. Coded serum samples were prospectively collected and analyzed for TA90-IC before and 2, 4, 8, 12, and 16 weeks after initiat ion of CancerVax therapy. TA90-IC seroconverters were those patients whose negative TA90-IC values (< .410) became positive (greater than or equal to .410) after initiation of CancerVax treatment. Results: Before CancerVax therapy, 51 patients had positive TA90-IC values and 168 patients had negative TA90-IC values. During CancerVax treatment, a ll 51 positive patients remained positive, 79 (47%) negative patients seroc onverted to positive, and 89 (53%) negative patients remained negative. Ser oconverters had higher 2-year rates of disease-free survival (59% vs. 32%; P < .006) and overall survival (78% vs. 63%; P < .02) than did patients who se TA90-IC values remained positive. Conclusions: CancerVax induces TA90-IC in melanoma patients with subclinica l disease. TA90-IC seroconverted patients have significantly improved disea se-free and overall survival compared with TA90-IC positive patients. TA90- IC is an important prognostic factor that can serve as a surrogate marker f or the clinical efficacy of CancerVax.