complex. Recombinant gene expression, toxicity, and the 
immunologic response to treatment is being evaluated. The 
objectives of this first human clinical trial using direct gene 
transfer were ( 1 ) to establish a safe and effective dose to 
introduce recombinant genes in vivo, ( 2 ) to confirm expression of 
the transduced gene, and (3) to analyze the immune response and 
potential therapeutic effects of this method of therapy. Based 
on animal studies, no toxicities had been readily apparent using 
these modes of direct gene transfer in vivo in short-term or 
long-term studies (1-3) . Taken together, these studies were 
intended to determine whether direct gene transfer was an 
appropriate form of treatment for malignancy. In addition, the 
data compiled from this study also provided an indication of 
whether this method of delivery could be appropriate for the 
treatment of a variety of other human diseases. 
In this study, another phase I clinical trial is proposed. 
The safety of this method and appropriate dosage in humans will 
be tested. Recombinant gene expression in vivo will be 
confirmed, and the specificity and mechanism of immune rejection 
will be defined. In subsequent phases, this response will be 
augmented by preimmunization and administration of cytokines, 
including tumor necrosis factor-a, interferon- 7 , or interleukin- 
2, or used in combination with adoptive transfer or TIL therapy. 
These studies will provide an alternative strategy for the 
immunotherapy of malignancy and allow definition of the mechanism 
of immune rejection of tumor cells. Adaptations of this method 
may also eventually be applied to the treatment of other human 
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Recombinant DNA Research, Volume 17 
