Studies of allogeneic tumor transplants: induced rejection of advanced tumors by immune alteration of recipients.
In the present experiments, a methylcholanthrene-induced sarcoma (S-702) of B10.D2 origin was found to grow rapidly in B6AF1 mice leading to the death of all recipients in 5 to 9 wk. Nevertheless, immunity to MHC antigens presented by the tumor was readily demonstrable in tumor-bearing mice by their responses to donor strain skin grafts until late in the course of tumor growth, when a nonspecific form of immune suppression developed. In addition, B6AF1 mice preimmunized by exposure to B10.D2 donor strain antigens did not permit tumor growth. Treatment of tumor-bearing B6AF1 mice with CY at 18 days, when the tumors measured over 12-mm in diameter, followed by the i.p. injection of B10.D2 lymphoid cells (at a dosage of from 1.2 to 2.5 X 10(8) cells) resulted in the complete regression of 100% of these large tumors. CY treatment combined with localized immune stimuli in the form of donor strain skin grafts or secondary tumor implants was incapable of producing a sufficiently heightened immune response to cause tumor rejection. A dose of CY temporarily retarded tumor growth in most mice, and in a minority of animals so treated (less than 25%) tumors regressed completely. In syngeneic (B10.D2) animals, CY also temporarily slowed tumor growth, but total regression was never observed. An effective B10.D2 cell inoculum could consist not only of living lymphoid cells but of irradiated (1000 rad) cells as well. Tumor cell suspensions (after irradiation, 10,000 rad) were also effective. These observations suggest local immune factors at the host-tumor interface may have been of importance in the survival of these allogeneic tumor transplants and that CY influenced this state, perhaps through an influence on suppressor cells, allowing subsequent administration of donor strain cellular antigens to induce an effective tumor rejection response.
D000818:Animals; D001666:Binding Sites, Antibody; D002471:Cell Transformation, Neoplastic / Q000276:immunology; D003520:Cyclophosphamide / Q000627:therapeutic use; D004306:Dose-Response Relationship, Immunologic; D005434:Flow Cytometry; D006085:Graft Survival; D006183:H-2 Antigens / Q000235:genetics; D017710:Lymphocyte Transfusion; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL / Q000276:immunology*; D009368:Neoplasm Transplantation; D012513:Sarcoma, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology*; D016038:Skin Transplantation
D006183:H-2 Antigens; D003520:Cyclophosphamide