recombinant TNF (supplied by the Cetus Corp. , Emeryville, California) adminis- 
tered in conjunction with IL-2 (3). No antitumor effects of TNF administration 
have been seen in humans. However, when high local concentrations of TNF are 
achieved at tumor sites by direct intralesional TNF rejection, tumor regression 
can be seen. In a paper by Bartsch et al . (Europ. J. Cancer and Clin. Oncol. 25: 
285-291, 1989) one of three melanoma patients who received intralesional Injections 
of TNF responded to treatment. In this study an additional patient with squamous 
cell cancer of the oropharnyx and a patient with malignant histocytoma also showed 
significant tumor shrinkage when TNF was injected into the tumor site. A double- 
blind randomized placebo controlled study of the intralesional injection of 
recombinant TNF-alpha was reported by Kahn et al . (Proc. Am. Soc. Clin. Oncol. 
8:4, 1989). In this study, one Kaposi's sarcoma lesion in each patient was 
injected with recombinant TNF and another Kaposi’s sarcoma lesion in the same 
patient was injected with the same volume of sterile saline. As reported by these 
authors "TNF reduced the cross sectional area of 12 of 13 (92%) of the injected 
KS lesions and caused the complete disappearance of two lesions. The placebo 
response rate was 7% with no complete response observed (p<0.01). There was no 
observed disease progression in any TNF treated lesion." These studies indicate 
that achieving high local concentrations at the tumor site can lead to tumor 
regression in humans. 
Extensive studies of the difference between the dramatic response of mice to 
the systemic injection of TNF and the lack of effect in humans have focused on 
the substantial differences in tolerance of mice and man to the administration 
of TNF. Tumor bearing mice can tolerate from 400-500 ug/kg TNF and these doses 
are required to mediate tumor regression; the administration of less TNF is far 
less effective (13). In contrast, the maximum tolerated dose of TNF in both 
Surgery Branch, NCI and other studies is approximately 8 ug/kg/day. Thus when 
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