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Characterization of the in Vitro and in Vivo Species Preference of Human and Murine Tumor Necrosis Factor-

Departments of Assay Development [S. M. K.], Molecular Biology and Immunology [B. B. A., T. E. E., S. M. M., I. S. F., M. A. P.], and Pharmacological Sciences [B. L. F.], Genentech, Inc., South San Francisco, California 94080

The species preference of human and murine tumor necrosis factor- (TNF-) was evaluated in human and murine systems for cytotoxic/cytostatic effects and receptor binding in vitro and murine systems for toxicity and antitumor activity in vivo. The in vitro cytotoxic/cytostatic effects of both species TNF- on human and murine cell lines as well as the receptor binding studies using ¹²⁵I-labeled recombinant human TNF- demonstrated homologous species preferences. Species preference of TNF- was also apparent in toxicity studies with BALB/c nu/nu and CB6F₁ mice, and antitumor responses of CB6F₁ mice to s.c. Meth A sarcoma implants. Moreover the growth of Meth A sarcoma implanted i.p. was not inhibited by either human or murine TNF-. These results are discussed in view of the potential for underestimation of the biological potency of TNF- from heterologous sources.

¹ To whom requests for reprints should be addressed, at Genentech, Inc., 460 Point San Bruno Boulevard, South San Francisco, CA 94080.

Received 3/13/87. Revised 7/27/87. Revised 11/ 6/87. Accepted 11/16/87.

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