Recombinant DMA Advisory Committee - 
He said that the early trials with LAK cells had prompted a search for a more effective 
cell type and that studies with tumor infiltrating lymphocytes (TILs) in mice served as a 
basis for attempts at human gene modification. These TILs were shown to be 
approximately 50 times as effective in mediating tumor regression in mice and thus a 
study of the effects of TILs in humans was undertaken. He summarized the data from 
the first 50 patients treated with TIL therapy. 
Dr. Rosenberg said the response rate of TIL treatment in the first 50 patients was twice 
that seen when LAK cells and IL-2 were administered, and that 38% of patients 
responded with an objective regression of their cancer (melanoma). The responses 
varied in duration from a few months to well over a year, but that there was room for 
improvement in the response rate. 
He said that a central aspect of the use of TILs for genetic modification resulted from 
studies showing that TILs accumulated in tumor deposits while not remaining in normal 
tissue. This resulted in the hypothesis that TILs could be used to deliver reagents to the 
tumor site that might increase the effectiveness of the TILs at those sites. This was the 
basis for the first protocol in which TILs with a neomycin-resistance gene were inserted 
into patients to study the long-term survival and distribution of TILs, the results of which 
had been presented previously to the RAC. This experiment, in which 10 patients were 
treated, showed that these TILs consistently circulated in the patients for three-four 
weeks, but that some patients had N2/TILs in their circulation out to 60 days post 
infusion. In fact, these cells were found in circulation up to 189 days in one patient. 
He noted that the patients all had advanced malignancy at multiple sites including liver, 
lung, brain and subcutaneous tissue and that their life expectancies did not exceed 90 
days. Two of the first five patients treated had objective responses. He cited one 
woman, 26 years of age, who had multiple tumor deposits in her lungs and soft palate 
who had undergone complete regression of her melanoma, and continues in complete 
regression now 18 months post-treatment. 
Dr. Rosenberg said that autopsies had been performed on three patients who had 
succumbed to their disease over 200 days post-transfer. Two of such autopsies had been 
analyzed and no evidence for residual cells was seen by PCR assay. 
Dr. Rosenberg stressed that there were no side effects noted in any patient due to the 
gene transfer. No evidence exists that any patient was ever exposed to replication- 
competent virus, either in cells tested, or in studies performed on lymphocytes or serum 
of patients after transfer. 
He said that the second phase of these studies was an attempt to insert genes that might 
improve therapeutic efficacy of the TILs, using the gene for tumor necrosis factor (TNF). 
Recombinant DNA Research, Volume 14 
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