1.0 
Introduction 
1.1 Rationale and Relationship to Previous Work 
This proposal represents an extension of a previously 
approved protocol submitted and approved by the Recombinant DNA 
Advisory Committee on February 10, 1992, entitled "Immunotherapy 
of Malignancy by In Vivo Gene Transfer into Tumors." Since the 
implementation of the first protocol, there have been four 
developments which have led to the modifications proposed in this 
study. The background and description of the previous trial is 
included in the appendix (1-5) . The previous trial has now been 
completed, and the conclusions have been summarized in the 
accompanying data. Briefly, the trial has demonstrated that 
recombinant gene expression can be achieved following direct gene 
transfer into melanoma in humans. In addition, there has been no 
evidence of toxicity from this treatment, and no antibody 
responses were detected to DNA as a result of this intervention. 
The clinical and immunologic responses are currently undergoing 
evaluation, and the status of these studies will be summarized at 
the RAC meeting; however, based on the findings of gene 
expression and lack of toxicity, we have felt that it is 
appropriate to pursue this general approach to the introduction 
of a foreign antigen into tumors in an effort to stimulate anti-s- 
tumor immunity. 
Since the initial trial, there have been advances in four 
areas of the gene transfer technology. In this protocol, we will 
incorporate these improvements into the protocol. Briefly, these 
improvements include: 
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Recombinant DNA Research, Volume 17 
