Immunochemotherapy of transplantable Moloney leukemia with cyclophosphamide and allogeneic spleen lymphocytes and reversal of graft-versus-host disease with alloantiserum

Abstract

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 donor-specific gamma-globulin titer 8 weeks postgrafting.