INCREASED IMMUNOGENICITY OF TUMORS BEARING MUTANT P53 AND P1A EPITOPES AFTER TRANSDUCTION OF B7-1 VIA RECOMBINANT ADENOVIRUS

The majority of human solid rumors are likely to express protein epito pes which can act as targets for cytotoxic T cells, but these are freq uently not effectively recognized. We tested whether the introduction of the costimulatory molecule B7-1 using a recombinant adenovirus (Ad- B7) can result in effective induction of epitope-specific immunity in two tumor models that express defined endogenous protein epitopes: D45 9, a fibroblast-derived cell line transfected with a human missense mu tant p53 (C to Y at position 135), and P815, a mastocytoma expressing the endogenous tumor epitope P1A. Under the conditions studied, both o f these tumors grow and kill their hosts without evidence of significa nt immune rejection. However, after transduction with the adenovirus c ontaining B7-1, both of these tumors lose tumorigenicity and elicit sp ecific cellular immunity to the mutant p53 epitope in D459 and P1A in P815. In addition, animals exposed to B7-transduced tumor cells were p rotected from subsequent challenge with nontransduced tumor. Adenoviru s has distinct advantages for this approach, as it has a high infectiv ity not requiring in vitro culture, low lyric potential, and transient expression of sufficient duration for immunologic effectiveness but w ithout significant concern over permanent genetic modification. We con clude that transduction of tumor cells with Ad-B7 can increase the imm unogenicity of endogenous protein epitopes and may represent a practic al therapeutic approach to systemic human cancers.