The Journal of Experimental Medicine
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Journal of Experimental Medicine, Vol 170, 1015-1020, Copyright © 1989 by Rockefeller University Press

ARTICLES

Passive immunization against tumor necrosis factor partially abrogates interleukin 2 toxicity

DL Fraker, HN Langstein and JA Norton
Surgical Metabolism Section, National Cancer Institute, Bethesda, Maryland 20892.

Passive immunization against TNF allowed non-tumor-bearing C3H/HEN mice and tumor-bearing C57BL/6 mice to tolerate significantly more doses of IL-2 before death (p less than 0.005 and p less than 0.001, respectively). The antitumor effect of IL-2 against both 3-d and 10-d pulmonary metastases was maintained in mice treated concurrently with neutralizing antibodies to TNF. In one experiment with 10-d pulmonary metastases, increased administration of IL-2 made possible by passive immunization against TNF significantly improved the antitumor response compared to equitoxic doses of IL-2 and control antibody. The results indicate that TNF is a mediator of IL-2 toxicity but contributes minimally to the antitumor effects of IL-2. Strategies to inhibit TNF may improve the therapeutic index of IL-2 as a neoplastic agent.
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