Because of these several improvements, we have submitted a 
protocol which proposes to incorporate these modifications in 
another phase I/II clinical trial to determine the safety and 
toxicity of this treatment. The study design and clinical 
endpoints remain almost identical to the previous trial, and are 
detailed in the following sections. 
1 . 2 Background 
A variety of genetic abnormalities arise in human cancer 
which contribute to neoplastic transformation and malignancy. 
Instability of the genome generates mutations which alter cell 
proliferation, angiogenesis, metastasis, and tumor 
immunogenicity . Despite a better understanding of the molecular 
basis of cancer, many malignancies remain resistant to 
traditional forms of treatment. The definition of tumor- 
associated genetic mutations, however, has heightened interest in 
cancer as a target for gene therapy. Immunotherapy has shown 
promise as a primary approach to the treatment of malignancy. 
Indeed, specific cancers, such as melanoma or renal cell 
carcinoma, are relatively more responsive to modulation of immune 
function, possibly because the immune system can be induced to 
recognize mutant gene products in these cells. Conventionally, 
approaches to immunotherapy have involved the administration of 
non-specific immunomodulating agents such as Bacillus Calmette- 
Guerin (BCG) , cytokines, and/or adoptive T cell transfer, which 
have shown promise in animal models (7-12) and in man (13-16). 
More recently, molecular genetic interventions have been designed 
in an attempt to improve the efficacy of immunotherapy. Human 
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