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Immunochemotherapy of Transplantable Moloney Leukemia with Cyclophosphamide and Allogeneic Spleen Lymphocytes and Reversal of Graft-versus-Host Disease with Alloantiserum¹

Microbiological Associates, Bethesda, Maryland 20016 [M. K., L. D. K.], and National Cancer Institute, NIH, Bethesda, Maryland 20014 [M. G., A. G.]

Histoincompatible (H-2) spleen cells from C57BL/6 mice that were sensitized with Moloney sarcoma virus caused fatal graft-versus-host disease in BALB/c mice when the cells were used in conjunction with an immunosuppressive, chemotherapeutic dose of cyclophosphamide to treat transplantable Moloney virus-induced leukemia. When antiserum against the donor spleen cells was administered 2 days after immunochemotherapy, graft-versus-host disease was prevented, but no immunotherapeutic effect was observed. When the antiserum was delayed for 3 days or more, lethal graft-versus-host disease occurred. Substitution of Moloney sarcoma virus-sensitized BALB/c x C57BL/6 F₁ (hereafter called CB6F₁) spleen cells for C57BL/6 cells, in conjunction with cyclophosphamide, "cured" 70% of the treated mice (accumulated value of two experiments). When anti-CB6F₁ serum (alloantiserum) was administered 2 days after immunochemotherapy, the immunotherapeutic effect was abolished. Alloantiserum was not able to reverse the immunotherapeutic effect 3 days postgrafting or later, and there resulted a high percentage of long-term survivors. About two-thirds of the cured mice had positive donorspecific -globulin titer 8 weeks postgrafting.

¹ This work was supported in part by Contract NO1-CM-33728 with Division of Cancer Treatment, National Cancer Institute, NIH, Department of Health, Education and Welfare, Bethesda, Md. 20014.

² To whom reprint requests should be addressed, at the Cancer Chemotherapy Department, Microbiological Associates, 5221 River Road, Bethesda, Md. 20016.

Received 8/26/74. Accepted 10/30/74.