Introduction: TA90 is a tumor-associated 90-kD glycoprotein antigen expressed on most melanoma cells, including those of CancerVax, a polyvalent allogeneic whole-cell vaccine. Previous studies have shown that a TA90 antigen-antibody immune complex (IC) in the serum of patients with melanoma is a marker of subclinical tumor burden and a strong prognostic factor. We hypothesized that the induction of TA90-IC during postoperative adjuvant CancerVax therapy might indicate vaccine-mediated immune destruction of subclinical melanoma 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 prospective 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 initiation of CancerVax therapy. TA90-IC seroconverters were those patients whose negative TA90-IC values (< .410) became positive (> or = .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, all 51 positive patients remained positive, 79 (47%) negative patients seroconverted to positive, and 89 (53%) negative patients remained negative. Seroconverters 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 whose TA90-IC values remained positive.
Conclusions: CancerVax induces TA90-IC in melanoma patients with subclinical disease. TA90-IC seroconverted patients have significantly improved disease-free and overall survival compared with TA90-IC positive patients. TA90-IC is an important prognostic factor that can serve as a surrogate marker for the clinical efficacy of CancerVax.