Abstract
C3H/He and CBA/T6T6 mice which share the H2k 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 107 BP8, but this dose, and more intensive treatment with this drug, fails to cure C3H mice.
(3) Injecting 125IUdR-labelled tumour cells and counting 125I 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 107 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.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Amiel J. L., Berardet M. Factor time for active immunotherapy after cytoreductive chemotherapy. Eur J Cancer. 1974 Feb;10(2):89–91. doi: 10.1016/0014-2964(74)90057-7. [DOI] [PubMed] [Google Scholar]
- Bomford R. Active specific immunotherapy of mouse methylcholanthrene induced tumours with Corynebacterium parvum and irradiated tumour cells. Br J Cancer. 1975 Nov;32(5):551–557. doi: 10.1038/bjc.1975.260. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chassoux D., MacLennan I. C., Munro T. R. Competition for cytotoxic immune capacity against a 'syngeneic' mouse tumour distributed at two sites. Int J Cancer. 1977 Jun 15;19(6):796–802. doi: 10.1002/ijc.2910190609. [DOI] [PubMed] [Google Scholar]
- Currie G. A. Active immunotherapy with Corynebacterium parvum and chemotherapy in murine fibrosarcomas. Br Med J. 1970 Feb 28;1(5695):541–544. doi: 10.1136/bmj.1.5695.541. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Falcão R. P., Sonis S., MacLennan I. C., Chassoux D., Davies A. J., Munro T. R. Assessment of drug sensitivity of human leukaemic myeloblasts. I. Labelling human myeloblasts with 125IUdR for survival studies in mice. Br J Cancer. 1977 Sep;36(3):297–306. doi: 10.1038/bjc.1977.193. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Finerty J. F., Krehl E. P. Cyclophosphamide pretreatment and protection against malaria. Infect Immun. 1976 Oct;14(4):1103–1105. doi: 10.1128/iai.14.4.1103-1105.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fisher B., Wolmark N., Rubin H., Saffer E. Further observations on the inhibition of tumor growth by Corynebacterium parvum with cyclophosphamide. I. Variation in administration of both agents. J Natl Cancer Inst. 1975 Nov;55(5):1147–1153. doi: 10.1093/jnci/55.5.1147. [DOI] [PubMed] [Google Scholar]
- Gotoda E., Sendo F., Hosokawa M., Kodama T., Kobayashi H. Combination of active and passive immunization and chemotherapy to transplantation of methylcholanthrene-induced tumor in WKA rats. Cancer Res. 1974 Aug;34(8):1947–1951. [PubMed] [Google Scholar]
- HADDOW A., ALEXANDER P. AN IMMUNOLOGICAL METHOD OF INCREASING THE SENSITIVITY OF PRIMARY SARCOMAS TO LOCAL IRRADIATION WITH X RAYS. Lancet. 1964 Feb 29;1(7331):452–457. doi: 10.1016/s0140-6736(64)90793-7. [DOI] [PubMed] [Google Scholar]
- HUGHES W. L., COMMERFORD S. L., GITLIN D., KRUEGER R. C., SCHULTZE B., SHAH V., REILLY P. DEOXYRIBONUCLEIC ACID METABOLISM IN VIVO: I. CELL PROLIFERATION AND DEATH AS MEASURED BY INCORPORATION AND ELIMINATION OF IODODEOXYURIDINE. Fed Proc. 1964 May-Jun;23:640–648. [PubMed] [Google Scholar]
- Hofer K. G., Prensky W., Hughes W. L. Death and metastatic distribution of tumor cells in mice monitored with 125I-iododeoxy-uridine. J Natl Cancer Inst. 1969 Oct;43(4):763–773. [PubMed] [Google Scholar]
- Mathé G., Pouillart P., Lapeyraque F. Active immunotherapy of L1210 leukaemia applied after the graft of tumour cells. Br J Cancer. 1969 Dec;23(4):814–824. doi: 10.1038/bjc.1969.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mihich E. Combined effects of chemotherapy and immunity against leukemia L1210 in DBA-2 mice. Cancer Res. 1969 Apr;29(4):848–854. [PubMed] [Google Scholar]
- Moore M., Williams D. E. Contribution of host immunity to cyclophosphamide therapy of a chemically-induced murine sarcoma. Int J Cancer. 1973 Mar 15;11(2):358–368. doi: 10.1002/ijc.2910110213. [DOI] [PubMed] [Google Scholar]
- Otterness I. G., Chang Y. H. Comparative study of cyclophosphamide, 6-mercaptopurine, azathiopurine and methotrexate. Relative effects on the humoral and the cellular immune response in the mouse. Clin Exp Immunol. 1976 Nov;26(2):346–354. [PMC free article] [PubMed] [Google Scholar]
- Pearson J. W., Chirigos M. A., Chaparas S. D., Sher N. A. Combined drug and immunostimulation therapy against a syngeneic murine leukemia. J Natl Cancer Inst. 1974 Feb;52(2):463–468. doi: 10.1093/jnci/52.2.463. [DOI] [PubMed] [Google Scholar]
- Porteous D. D., Munro T. R. The kinetics of the killing of mouse tumour cells in vivo by immune responses. Int J Cancer. 1972 Jul 15;10(1):112–117. doi: 10.1002/ijc.2910100115. [DOI] [PubMed] [Google Scholar]
- Ramshaw I. A., Bretscher P. A., Parish C. R. Regulation of the immune response. I. Suppression of delayed-type hypersensitivity by T cells from mice expressing humoral immunity. Eur J Immunol. 1976 Oct;6(10):674–679. doi: 10.1002/eji.1830061003. [DOI] [PubMed] [Google Scholar]