This project is a continuation of our current studies on the heterotransplantation of human malignancies in immunodeficient animals, namely athymic (nude) and asplenic-athymic (lasat) mice. Chronic myelogenous leukemia (CML) cells with the Philadelphia chromosome from the cell line K-562 proliferate forming solid tumors (myelosarcomas) in nude mice associated with extensive metastatic proliferation when transplanted in lasat mice. The treatment of mice with xenoantisera to K-562 cells suppressed the growth of myelosarcomas. On the basis of these findings we propose to use the human cancer cell-animal tumor systems described above as models for the formation and subsequent growth of solid tumors with the emphasis on the conditions of host and/or the malignant cells required for local growth and metastatic proliferation. The specific aims are: 1) to continue our current studies on the heterotransplantation of K-562 cells, 2) to continue and improve the treatment of myelosarcomas and metastases made of K-562 leukemia cells with specific antibody to K-562 cells, 3) to determine the mechanisms of action of the successful passive immunotherapy for myelosarcomas and metastatic proliferations of K-562 cells, 4) to develop drug-antibody conjugates for the treatment of mice bearing myelosarcomas and metastases, 5) to determine whether or not the natural cytotoxicity of nude mice is a major tumoricidal mechanism preventing the local growth and metastatic proliferation of myelosarcomas and other solid tumors of human origin mentioned in the following aim, 6) to develop new procedures for the heterotransplantation of human lung, breast and colorectal carcinomas, melanomas and the terminal blastic crisis of a CML. These malignancies are the primary targets of concern because there is no reliable treatment, are the most common type of cancer and/or very difficult to transplant in nude mice, and 7) to treat mice bearing human tumors with current and/or new therapeutic agents other than xenoantisera and antibody-drug conjugates. We propose various innovative approaches and novel ideas for the heterotransplantation of human malignancies.