Mediation of cytotoxic immune responses against human tumor-associated antigens by xenogeneic immune RNA.

Xenogeneic immune RNA (I-RNA), extracted from the lymphoid organs of sheep or guinea pigs immunized with human tumor cells, mediated in vitro cytotoxic immune responses that were directed specifically against tumor-associated antigens of human tumor target cells. Normal human peripheral blood lymphocytes from healthy donors became markedly more cytotoxic for human tumor target cells after being incubated with I-RNA extracted from the lymphoid organs of animals that had been immunized with that particular tumor. Gastric carcinoma, malignant melanoma, and carcinoma of the breast were studied. Lymphocytes incubated with RNA from animals immunized with only complete Freund's adjuvant evidenced no increased cytotoxic activity. RNA extracted from the lymphoid organs of animals immunized with normal skin fibroblasts that were autologous to the immunizing tumor, when incubated with normal allogeneic lymphocytes, also mediated cytotoxic immune reactions against tumor target cells. These immune responses probably were directed principally against normal transplantation antigens. However, when lymphocytes that were autologous to the immunizing tumor and/or the tumor target cells were incubated with RNA from animals immunized with autologous normal fibroblasts, cytotoxicity did not increase. Only I-RNA extracted from donor animals specifically immunized with tumor cells mediated cytotoxic antitumor immune responses when incubated with autologous lymphocytes.