Immune RNA therapy as an effective adjuvant immunotherapy after surgery: an animal model

Transfer of tumor immunity as adjuvant cancer therapy has been a topic of intense interest. We have examined the efficacy of various combinations of surgery, xenogeneic immune RNA, xenogeneic normal RNA, tumor vaccine, and nonspecific splenocytes as adjuvant therapy for B16 melanoma in the C57BL/6J mouse system. B16 melanoma was transplanted by trocar into the right hind limb of 6-week-old mice. The tumors were readily palpable on the ninth day posttransplantation. The tumors were amputated at that time under mild anesthesia. Immune RNA was prepared by hot phenol extraction from immune sheep spleens. Various combinations of immune RNA, normal RNA, and tumor antigen, with or without normal mouse spleen cells, were administered every other day for a total of 10 injections. The survival and mode of death was followed up to 120 days. All mice without any treatment died within 30 days. Immunotherapy had no effect on the survival of mice that did not have surgical therapy. Individual group comparisons between mice that underwent surgery only and mice that had surgery plus immune RNA immunotherapy revealed a striking statistical improvement (P less than 0.01). Comparing all groups that received amputation plus various combinations of adjuvant immunotherapy showed no statistical difference in survival. However, immune RNA appears somewhat superior to normal RNA or antigen only. It appears that adjuvant immune RNA immunotherapy following surgical excision in the B16 melanoma model significantly improves survival and retards the spread of metastases.