Faculty Bibliography

We report a statistically significant increase in tumor-infiltrating lymphocytes in subcutaneous melanoma metastases removed from patients immunized with a melanoma vaccine. Dense cellular infiltrates were seen in 10 of 11 nodules from vaccine-immunized patients, compared with 9 of 22 nodules from non-immunized patients (p = 0.02). Furthermore, these dense lymphocytic collections more frequently infiltrated the body of tumor nodules from immunized patients, whereas in non-immunized patients, lymphocytes were more often present only in the dermal tissue at the periphery of the nodule. Thus, allogeneic melanoma vaccines may augment immune responses to a patient's own tumor

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