Sequence dependence of administration of human recombinant tumor necrosis factor and interleukin-2 in murine tumor therapy.
Simultaneous administration of recombinant human tumor necrosis factor (rhTNF) and interleukin-2 (rhIL-2) has been shown to block tumor take in murine models. We investigated the effects of sequence and schedule of administration as a function of tumor burden with two tumor models (B16 and Meth A). rhTNF followed by rhIL-2 had extraordinary antitumor efficacy, but rhIL-2 followed by rhTNF was much less effective. Sequential rhTNF/rhIL-2 therapy resulted in complete tumor regression, whereas simultaneous therapy resulted in complete tumor regression, whereas simultaneous therapy resulted in only reduced growth rate. Experiments with genetically immunodeficient mice suggested that T cell factors may be required for synergistic antitumor activity.
Department of Pharmacology, Cetus Corporation, Emeryville, CA 94608.
R J
RJ
Zimmerman
S
S
Gauny
A
A
Chan
P
P
Landre
J L
JL
Winkelhake
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols; D004334:Drug Administration Schedule; D004357:Drug Synergism; D007153:Immunologic Deficiency Syndromes / Q000276:immunology; D007376:Interleukin-2 / Q000008:administration & dosage*; D051379:Mice; D009374:Neoplasms, Experimental / Q000628:therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*
D007376:Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha