performed to obtain lymphocytes for activation with anti-CD3 monoclonal antibody (OKT3) 
and expansion in IL-2 in vitro. After in vitro activation, these lymphocytes will be adoptively 
transferred intravenously to the patient followed by the administration of IL-2 (360,000 IU i.v. 
every 8 h. for 5 days). Fifteen patients will be treated to gain sufficient information regarding 
toxicity, antitumor reactivity and immunologic function. 
2.0 OBJECTIVES 
Our laboratory has described a new method of generating sensitized T cells for 
adoptive immunotherapy utilizing autologous tumor cells genetically modified to secrete IL-4. 
In preclinical studies, the in vivo administration of these tumor cells has been found to elicit 
sensitized T cells in the draining lymph nodes (LN) against a poorly immunogenic tumor. 
The subsequent in vitro activation of these LN cells by anti-CD3 mAb and IL-2 has resulted in 
the generation of T cells capable of mediating regression of established parental tumor 
metastases. These preclinical studies have formed the basis for a clinical evaluation of 
similarly derived T cells for patients with advanced melanoma. The objectives of this study 
are: 
2.1 To assess the feasibility and toxicity of adoptive T cell immunotherapy of 
melanoma with anti-CD3/IL-2 activated LN cells that are primed in vivo with IL-4 
modified tumor cells. 
2.2 To evaluate the antitumor efficacy and in vivo immunological reactivity of 
patients receiving adoptively transferred T cells. 
2.3 To investigate the in vitro immunological reactivities of the activated T cells that 
might correlate with their in vivo antitumor function. 
3.0 BACKGROUND AND RATIONALE 
Adoptive immunotherapy is defined as the transfer of antitumor reactive cells to the 
tumor-bearing host which will directly or indirectly mediate the regression of tumor. The 
therapeutic efficacy of adoptive immunotherapy of cancer with sensitized T lymphocytes is 
well-documented in animal studies. The application of this approach for the treatment of 
human cancer poses many theoretical and technical difficulties since it requires the 
generation of large quantities of antitumor reactive lymphocytes from cancer patients. 
Despite such limitations, many observations established in animal models of adoptive 
immunotherapy have been implemented in clinical trials with encouraging results. The 
demonstration of regression of solid tumors in man following the adoptive transfer of 
lymphokine-activated killer (LAK) cells or tumor-infiltrating lymphocytes (TIL) in conjunction 
with IL-2 has established that cellular therapy is a feasible alternative in treating cancers and 
has encouraged the search for more potent effector cells (1 ,2). 
3.1 Animal studies characterizing the immune T cell response in tumor- 
draining LN 
In spite of the demonstration that many animal tumors possess tumor-specific antigens 
which are capable of immunizing syngeneic hosts to reject a challenge of an otherwise lethal 
dose of tumor cells, antigenic tumors often grow in their immunocompetent hosts. 
Apparently, during progressive tumor growth, the innate immune response is insufficient due 
to the weakness of the antigen and/or the occurrence of tumor-induced immunosuppression. 
Using several immunogenic tumors, we have demonstrated that LN draining a progressively 
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