The aim of the proposed research is to study in animal tumor models the immunotherapy of cancer with "Immune" RNA and to optimize immunotherapeutic regimens to provide for maximum efficacy. These studies will provide a basis for subsequent clinical trials in the immunotherapy of human cancer with "Immune" RNA. Our studies employ a spontaneously metastasizing breast adenocarcinoma in inbred Fischer rats. Following transplantation, when local tumors are excised most rats die of metastases to the lung and other organs. Types of "Immune" RNA studied will be: 1) xenogeneic "Immune" RNA extracted from the lymphoid organs of guinea pigs immunized with 13762 cells, and 2) syngeneic "Immune" RNA extracted from the lymphoid organs of rats bearing growing 13762 transplants. Control RNA preparations will be extracted from the lymphoid organs of guinea pigs immunized with: 1) a non-crossreacting chemically-induced Fischer sarcoma, 2) a pool of normal Fischer tissues, and 3) complete Freund's adjuvant only. For some experiments "Immune" RNA preparations will be treated with either RNase prior to use. Controls for the syngeneic "Immune" RNA will consist of RNA from the lymphoid organs of rats bearing growing transplants of antigenically different Fischer tumor, and RNA from the lymphoid organs of normal Fischer rats. Two treatment methods will be employed: 1) direct systemic administration of "Immune" RNA in a vehicle containing an Rnase inhibitor, and 2) direct systemic administration of "Immune" RNA without an Rnase inhibitor, sodium dextran sulfate. Control groups are treated with 1) RNA from the lymphoid of pigs immunized with normal Fischer tissues, 2) specific "Immune" RNA treated with RNase prior to use in experimental animals, 3) specific "Immune" RNA in a solution from which the RNase inhibitor has been omitted, and 4) RNA prepared from the lymphoid organs of guinea pigs immunized with a different tumor.