Adenoviral transfer of xenogeneic MHC class I gene results in loss of tumorigenicity and inhibition of tumor growth

The immune system confers protection against a variety of pathogens and con tributes to the destruction of neoplastic cells. Foreign major histocompati bility complex (MHC) protein serves as a potent stimulus to the immune syst em. In this report, a mouse H-2K(b) gene was introduced into two poorly imm unogenic tumor cell lines, a mouse colonic carcinoma cell line, MCA-26 (H-2 K-d), and a rat mammalian carcinoma cell line, LN-4, in an effort to stimu late tumor rejection. Our results showed that the expression of xenogeneic MHC class I antigen completely abolished the LN-4 tumorigenicity in rats, w hereas the expression of allogeneic MHC class I antigen only partially redu ced the MCA-26 tumorigenicity in mice. Rats with tumor regression of LN-4/H -2K(b) developed a T helper type 1-dominant response, whereas rats with LN- 4 tumor growth developed a T helper type 2-dominant response. The immunized rats that experienced LN-4/H-2Kb tumor regression further developed protec tive immunity against a subsequent challenge of LN-4 cells. This protective immunity was mediated by the LN-4 tumor-specific cellular immune response against both the transduced and the parental LN-4 cells. Recombinant adenov iral vectors are highly efficient at in vitro and in vivo gene delivery. Th e LN4 cells transfected with the recombinant adenovirus AdV-H-2K(b) in vitr o expressed the cell surface H-2K(b) molecule by fluorescence-activated cel l sorter analysis. Adenovirus-mediated H-2K(b) gene transfer in vivo can fu rther significantly inhibit pre-established LN-4 tumors. Those rats with co mplete tumor regression further developed protective immunity against the s ubsequent challenge of a parental LN-4 tumor. Therefore, our study indicate s that the adenovirus-mediated transfer of xenogeneic MHC class I gene may be an effective alternative to the current protocol of cancer gene therapy in which the allogeneic MHC class I gene is used.