Immune Response Against Large Tumors Eradicated by Treatment with Cyclophosphamide and IL-12

  • Tsung K
  • Meko J
  • Tsung Y
  • et al.
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Abstract

Previous studies have demonstrated eradication of small (4–8 mm) established murine MCA207 sarcomas by treatment with systemic IL-12. Analysis of the mechanism has revealed a cellular and molecular immune response at the tumor typical of a Th1 cell-mediated, macrophage-effected, delayed-type hypersensitivity (DTH) response. In the current study we investigate the immune response against long term established, large MCA207 tumors induced by combined treatment with IL-12 and cyclophosphamide (Cy), an agent known to potentiate the DTH response. Our results demonstrate that s.c. large MCA207 tumors (15–20 mm) that are refractory to treatment by either IL-12 or Cy alone can be completely eradicated by the combination of Cy and IL-12. IL-12 is apparently the only cytokine capable of mediating tumor eradication, and the effect is dependent on IFN-γ. The contribution of Cy is probably due to immunopotentiation of DTH rather than to direct cytotoxicity to the tumor. The regression of these large tumors takes >4 wk and, in many cases, is self-sustained, in that little or no additional IL-12 is needed beyond the initial week of administration. Analysis of the cellular and molecular events at the tumor site suggests that the mechanism is a Th1-mediated antitumor immune response.

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Tsung, K., Meko, J. B., Tsung, Y. L., Peplinski, G. R., & Norton, J. A. (1998). Immune Response Against Large Tumors Eradicated by Treatment with Cyclophosphamide and IL-12. The Journal of Immunology, 160(3), 1369–1377. https://doi.org/10.4049/jimmunol.160.3.1369

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