Faculty Bibliography

Fifty-five patients with Stage II (36 patients) or Stage III (19 patients) malignant melanoma confirmed histologically received adjuvant immunotherapy with a polyvalent melanoma antigen vaccine to evaluate toxicity and immunogenicity. There was no toxicity. Antibody and/or cellular immune responses to melanoma were induced more frequently in Stage II (36 patients [69%]) than Stage III (19 patients [53%]) disease. The ability of different immunization schedules, alum, or pretreatment with low-dose cyclophosphamide to potentiate immunogenicity was compared after 2 months of immunization. Immunization biweekly with a fixed intermediate dose of vaccine was more immunogenic than immunization weekly with escalating vaccine doses. Alum increased the intensity of cellular responses slightly, whereas pretreatment with cyclophosphamide augmented both the incidence and intensity of cellular immune responses slightly. However, these changes did not reach statistical significance. There was a reciprocal relationship between the induction of humoral and cellular immune responses. These results show that (1) active immunotherapy with a polyvalent melanoma vaccine is safe in patients with minimal disease, (2) the vaccine augments immunity to melanoma in many, but not all, patients, and (3) several immunization strategies failed to potentiate immunogenicity significantly

To determine if a soluble mediator of antigenic competition could be demonstrated in vivo, various groups of mice received implants of intraperitoneal Millipore diffusion chambers containing normal spleen cells and sheep erythrocytes (SRC). Priming and boosting the chamber hosts so that a vigorous secondary immune response to horse erythrocytes (HoRC) coincided with chamber implantation resulted in the suppression of the anti-SRC response of the chamber-enclosed cells. Similarly, passive immunization of the chamber hosts with SRC-absorbed anti-HoRC hyperimmune serum suppressed the response of the chamber-enclosed cells to SRC. Thus, serum from hyperimmune mice contains a humoral suppressor substance which mediates antigenic competition.