tumor infiltrating lymphocytes have shown efficacy in animal 
models and human trials. We have developed a model for the 
immunotherapy of malignancy, based on a novel method to stimulate 
an immune response against tumor cells by genetic modification in 
vivo . This approach differs from previous methods in which tumor 
cells are propagated, modified, and selected in vitro . We have 
recently shown that recombinant genes can be introduced and 
expressed at specific anatomic sites in vivo by direct gene 
transfer into vessels. This method has been adapted to deliver 
recombinant genes to tumor cells in vivo . We have introduced 
genes encoding a highly immunogenic molecule, an allogeneic class 
I major histocompatibility complex (MHC) glycoprotein, into 
transplantable mouse tumors. When the foreign MHC gene has been 
delivered into tumors in vivo , it induces cytolytic T cells 
against this antigen and has produced partial tumor regressions. 
More importantly, this treatment elicits a cytolytic T cell 
response against parental unmodified tumor cells. This approach 
therefore provides an alternative approach to the immunotherapy 
of malignancy. It can be used alone or in combination with other 
genes, including cytokines, to cause tumor regression. 
In this study, a 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 
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