Characterization of the in vitro and in vivo species preference of human and murine tumor necrosis factor-alpha.
The species preference of human and murine tumor necrosis factor-alpha (TNF-alpha) 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-alpha on human and murine cell lines as well as the receptor binding studies using 125I-labeled recombinant human TNF-alpha demonstrated homologous species preferences. Species preference of TNF-alpha 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-alpha. These results are discussed in view of the potential for underestimation of the biological potency of TNF-alpha from heterologous sources.
Kramer
S M
SM
Department of Assay Development, Genentech, Inc., South San Francisco, California 94080.
Aggarwal
B B
BB
Eessalu
T E
TE
McCabe
S M
SM
Ferraiolo
B L
BL
Figari
I S
IS
Palladino
M A
MA
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D051379:Mice; D011956:Receptors, Cell Surface / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins / Q000494:pharmacology; D013045:Species Specificity; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*
D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha