6. Confirmation was requested that melanoma, and not 
adenocarcinoma, will be treated. Although it is a potential 
target of future studies, adenocarcinoma will not be included for 
the initial phase I studies. A confirmatory letter has been sent 
to our local IRB. 
7. Additional studies have been taken to document the 
mechanism of tumor protection in this model system. Recent 
studies have been performed using direct gene transfer in nude 
mice with the MCA 106 fibrosarcoma. The introduction of H-2K S 
into tumors within these animals does not result in any tumor 
protection, further substantiating the T cell dependency of this 
response. Finally, an HLA-B7 expression vector containing a 
deletion in the al and a2 domains of the class I MHC genes do not 
confer an anti-tumor response. These results are described in 
the revised "Preliminary Data" section (Section 13), as are 
additional data regarding expression in human melanoma cells and 
systemic tumor immunity presented during the November 21 meeting. 
This proposal is now presented in modified form to address 
the concerns of the Human Gene Therapy Subcommittee. The most 
recent modifications are indicated in bold for the convenience of 
the reviewers. Previous modifications are summarized in Section 
24, Appendix VI. 
1 . 2 Background 
Immunotherapy has shown promise as an adjuvant approach to 
the treatment of malignancy. Both cytolytic T cells and 
lymphokines can facilitate tumor cell destruction, and strategies 
to enhance tumor regression by administration of cytokines or 
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