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Methods of Immunosuppression for Study of Growth and Lung Colony Formation by Human Tumor Cells in Mice¹

Departments of Medicine and Medical Biophysics, Ontario Cancer Institute and University of Toronto, 500 Sherbourne Street, Toronto, Ontario, Canada M4X 1K9

Mice that are immune-suppressed by thymectomy and by sequential treatment with 1-ß-D-arabinofuranosylcytosine and whole body irradiation may be used as hosts for generation of human tumor xenografts. We have studied the effect of various additional methods of immune suppression on the formation of tumors after i.m. injection and on the formation of lung colonies after i.v. injection with the human MGH-U1 bladder cancer cell line. Success of transplantation was improved by treatment of immune-suppressed animals with either heterologous antilymphocyte serum or a monoclonal anti-Thy-1.2 antibody. Success of lung colony formation was also improved by antilymphocyte serum but not by monoclonal anti-Thy-1.2 antibody. Admixture of heavily irradiated cells (10⁶) to the viable inoculum of tumor cells in addition to antilymphocyte serum treatment improved the success of i.m. transplantation but not that of lung colony formation. Treatment with corticosteroids or treatment with carrageenan to suppress macrophage activity added toxicity and did not improve the success of xenografting. Immune suppression decreased the natural killer cell activity of normal mice and treatment with antiinterferon to further suppress natural killer cells may also enhance xenograft formation. Administration of cyclosporin A to normal mice allowed the growth of a single xenograft but was not a useful method for immuno-suppression. The success of xenografting into immune-deprived mice was superior to that for two strains of nude mice maintained in our laboratory, and i.v. injection of tumor cells did not lead to lung colonies in these nude mice. Immune-deprived mice are a useful alternative to nude mice for the study of xenografts derived from human tumor cell lines and may allow the study of experimental lung metastases.

¹ Supported by a National Cancer Institute of Canada Fellowship to A.K. and by NIH Grant CA 29526 awarded through the National Bladder Cancer Project.

² To whom requests for reprints should be addressed.

Received 8/ 9/85. Revised 12/ 6/85. Accepted 12/27/85.