Xenotransplantation of human lymphoid malignancies is optimized in mice with multiple immunologic defects

While it is known that mice with genetic immune defects are useful for esta blishing durable engraftment of human tumor xenografts, the relative role o f components of host innate and adoptive immunity in engraftment has not be en determined. We directly compared the ability of four strains of genetica lly immunodeficient mice (NOD/SCID, SCID, Nude and Rag-1-deficient) to succ essfully engraft and support the human cell lines Daudi, Raji, Namalwa and Molt-4 as subcutaneous tumors. We additionally examined the effect of furth er immunosuppression of the mice by whole body irradiation at a dose of 600 cGy for Nude and Rag-1 and 300 cGy for SCID mice and by administration of anti-natural killer (asialo-GM1) antibody on tumor growth. Mice with each o f the defects supported xenografts to varying degrees. We found differences in growth characteristics in the cell lines tested, with Namalwa consisten tly producing the largest tumors. With all cell lines studied, optimal grow th was achieved using NOD/SCID mice. Overall, tumor growth was somewhat enh anced by pretreatment with radiation with little additional benefit from th e addition of anti-asialo-GM1 antibody. The importance of multiple componen ts of the innate and adoptive immune system in xenotransplantation were bes t demonstrated when results in untreated NOD/SCID mice were compared to SCI D, nude and RAG-l-deficient mice. The NOD/SCID mouse with or without additi onal immunosuppression provides the optimal model for the study of the biol ogy and treatment of human leukemias and lymphomas.