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Department of Surgery, University of California, San Francisco, VA Medical Center at San Francisco, San Francisco, CA 94121
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-
. 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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