I. 
OBJECTIVES 
To evaluate the possible therapeutic efficacy of the injection of 
autologous cancer cells modified by insertion of the gene for interleukin-2 
into patients with advanced cancer. 
II. INTRODUCTION AND RATIONALE 
1. Cell transfer therapy using TIL . Research in the Surgery Branch, 
NCI has been directed toward developing new immunotherapies for the treatment 
of patients with cancer (1-5). Based on extensive animal experimentation we 
developed treatment approaches using the administration of high dose 
interleukin-2 (IL-2) alone or in conjunction with the adoptive transfer of 
lymphokine activated killer (LAK) cells in patients with advanced cancer (1). 
We have now treated 178 patients using LAK cells in conjunction with IL-2 and 
136 patients with high dose IL-2 alone (3). The results of the treatment of 
these 314 patients are shown in Table 1 and Table 2. These studies have 
demonstrated that the administration of high dose IL-2, either alone or in 
conjunction with LAK cells can result in the regression of advanced cancer in 
some patients. Approximately 10% of patients with metastatic renal cell 
cancer and melanoma will undergo a complete regression of cancer following 
treatment with LAK cells and IL-2 and an additional 10-25% of patients will 
undergo an objective partial remission. 
In an attempt to improve upon these results, we identified and 
characterized a more potent type of killer cell called the tumor infiltrating 
lymphocyte (TIL) (6). These cells are cytolytic T lymphocytes. In both mice 
and human, TIL can develop the ability to specifically lyse the syngeneic or 
autologous tumor and not normal cells or allogeneic tumors (7,8). We 
demonstrated that TIL were from 50-100 times more potent on a per cell basis 
than were LAK cells in mediating the regression of established cancer in 
several murine tumor models (6). These animal experiments led to clinical 
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- 
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