Analysis of synergy between cyclophosphamide therapy and immunity against a mouse tumour

Abstract

C3H/He and CBA/T6T6 mice which share the H2(k) haplotype were compared for their capacity to survive challenges with the C3H-derived fibrosarcoma BP8. It was found:(1) The tumour grows at the same rate with the same median survival time in matched groups of non-immunized mice from both strains after i.p. injection of tumour cells.(2) Cyclophosphamide (Cyclo) at 10 mg/kg will cure CBA mice which have received i.p. injections of 10(7) BP8, but this dose, and more intensive treatment with this drug, fails to cure C3H mice.(3) Injecting (125)IUdR-labelled tumour cells and counting (125)I loss by whole-mouse counting shows that the cytotoxic effect of Cyclo against BP8 is similar in the 2 mouse strains.(4) Cyclo itself does not cure CBA mice, for viable tumour cells are recoverable from the peritoneal cavity 10 days after CBA mice have received 10(7) BP8 followed by 10 mg/kg Cyclo.(5) CBA mice cured of BP8 ascites by Cyclo treatment will reject further i.p. inocula of BP8.(6) The strength of immunity induced by irradiated BP8 cells was directly related to the length of exposure to this antigen. An important aspect of Cyclo treatment is that it prolongs the period during which immunity may develop.(7) Immunization of CBA mice with heavily irradiated BP8, with or without Cyclo, failed to show that Cyclo depressed the capacity of CBA mice to develop cytotoxic immunity. There was some indication that animals immunized with irradiated cells plus drug did better than those with irradiated cells alone.(8) A single injection of irradiated BP8 cells into CBA mice induced weak cytotoxic immunity, as assessed by destruction of a subsequent challenge with BP8, but these mice died from tumour more rapidly than non-immunized controls. It is suggested from these data that immunological enhancement may not always be due to blocking of cytotoxic immunity.