eight percent of melanoma patients underwent an objective regression of their 
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 antitumor activity of the TIL transfer. 
To further study the distribution and survival of TIL we have performed 
studies of the retroviral transduction of the gene coding for neomycin 
resistance into TIL (11) and the subsequent infusion of these TIL into 10 
autologous patients with advanced cancer (12). Extensive studies have been 
conducted on the first five patients and they are presented in Tables 4 and 5 
and Figure 1. No toxicities of any kind could be attributed to the gene 
modification of the TIL. The expected toxicities associated with the 
concomitant administration of IL-2 were seen. Patients received up to 1.45 x 
10 n gene transduced TIL populations. The percent of cells transduced in these 
populations varied between one and 11%. In all cases, integration and 
expression of the NeoR gene was demonstrated. As shown in Figure 1, gene 
modified TIL could be detected at tumor deposits as long as 64 days after gene 
transduction. 
All safety studies performed in these patients showed no evidence of 
exposure to replication competent virus. 3T3 amplification and S+/L- assays 
revealed no replication competent virus present in the TIL at the time they 
were infused. Polymerase chain reaction analysis for the viral envelope gene 
and reverse transcriptase assay of the gene-modified TIL culture were also 
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Recombinant DNA Research, Volume 15 
