trials of the use of TIL In humans (5). The results of the treatment of 50 
patients with metastatic malignant melanoma are shown in Table 3. Thirty- 
eight percent of melanoma patients underwent an objective regression of theif 
cancer, however, the duration of responses has been variable and in many cases 
this response has been of short duration. 
Extensive studies have been performed in the Surgery Branch, NCI to study 
the characteristics of human TIL and the mechanism of action of these cells in 
patients (9), In an attempt to study the traffic of TIL following cell infusion, 
19 infusions of TIL labelled with Indium-111 were given to 18 patients and the 
distribution of these cells assessed using gamma camera imaging and sequential 
biopsies (10). Clear tumor localization of TIL was seen on 13 of 18 nuclear 
scan series and sequential biopsy data confirmed the homing of TIL to tumor 
deposits. These findings raised the possibility that TIL might be used as 
vehicles to deliver, to the tumor site, molecules that might enhance the anti- 
tumor activity of the TIL transfer. 
2. Anti-tumor effects of tumor necrosis factor . Extensive animal 
research in the Surgery Branch, NCI, and in many other groups studying the 
administration of recombinant tumor necrosis factor (TNF) have demonstrated 
that the injection of recombinant TNF can mediate the necrosis and regression 
of a variety of established experimental murine cancers (11-13). The combined 
administration of TNF and IL-2 mediated far greater antitumor effects against 
subcutaneous and liver tumors than either cytokine alone (14). The exact 
mechanisms of TNF antitumor effects are not clearly understood, although it 
appears that TNF has a significant effect on the vascular supply of tumors 
(13). Membrane-bound TNF may be Involved in direct tumor lysis as well (15). 
These animal experiments have led to extensive tests of recombinant human TNF 
administered to humans with advanced cancer (3,16-19). In the Surgery Branch, 
NCI, we treated 38 patients with advanced cancer using escalating doses of 
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