INDUCTION OF A CYTOLYTIC T-CELL RESPONSE IN MICE WITH A RECOMBINANT ADENOVIRUS CODING FOR TUMOR-ANTIGEN P815A

We investigated the efficacy of a recombinant adenovirus int inducing a cytolytic T-lymphocyte (CTL) response in mice: against tumor antigen P815A, which is present on mouse mastocytoma P815. The recombinant ad enoviral vector (Adeno.P1A) contained the sequence coding for the anti genic: nonapeptide which binds to the H-2.L(d) molecule to form antige n P815A. We verified that murine cells infected in vitro with Adeno.P1 A were lysed by an anti-P815A CTL clone. Mice then received a single i ntradermal injection of Adeno.P1A, and after a few weeks their spleen cells were stimulated in vitro with tumor cells expressing antigen P81 5A. An anti-P815A CTL. response was observed with the spleen lymphocyt es of nearly all the mice, providing the lymphocytes were re-stimulate d in vitro with cells expressing both P815A and co-stimulatory molecul e B7.1. When the stimulatory cells did not express B7.1, a specific CT L response was observed in only 45% of the mice, and it was less inten se. The Adeno.P1A viral vector was unable to raise an anti-P815A respo nse in mice that had been previously infected with a recombinant adeno virus carrying the B-galactosidase gene or with a defective adenovirus . We conclude that adenoviral vectors may be very useful for the primi ng of cytolytic T-cell responses directed against human tumor antigens . Other modes of immunization may be necessary to boost the responses induced with adenoviral vectors. (C) 1996 Wiley-Liss, Inc.