Xenotransplantation in immunosuppressed nude mice of human solid tumors and acute leukemias directly from patients or in vitro cell lines.

Abstract

Athymic nude (nu/nu) mice are widely employed for the heterotransplantation of human tumor cell lines established in vitro and tumor cells directly grafted from patients. By contrast, hemopoietic malignancies have consistently proved difficult to transplant and well-characterized human leukemias suitable for studies in nude mice are scarce. We report here our experience with subcutaneous xenotransplantation of human neoplastic cells into nu/nu mice immunosuppressed through sublethal irradiation and splenectomy (SI-nu/nu) and with an additional injection of anti-Asialo-GM1 antibodies (SIA-nu/nu) in order to eliminate natural killer activity. Thirteen out of 16 continuous cell lines established in vitro from solid tumors and 7 out of 14 human tumors obtained from fragments of surgical specimens formed a progressively growing tumor in SI-nu/nu mice. Six out of 8 in vitro established human leukemic cell lines and 5 out of 18 neoplastic hematopoietic cells directly xenotransplanted from the patient grew SIA-nu/nu mice. When the membrane and chromosome markers of neoplastic cells that grew into the mice were evaluated, only marginal differences with those of the original tumors were found. In addition, when interfering factors alter the histological aspect of the primary tumor, xenotransplantation may also be of some help in histological diagnosis. By using SI- and SIA-nu/nu mice, it is thus possible to build up several new in vivo experimental systems with fresh human tumors that may be of value in studying the efficacy of differentiation factors and immunological maneuvers on the in vivo growth of human tumors.