EXPRESSION OF 2 H-2K GENES, SYNGENEIC AND ALLOGENEIC, AS A STRATEGY FOR POTENTIATING IMMUNE RECOGNITION OF TUMOR-CELLS

Metastatic clones of some tumors manifest an impaired expression of cl ass I major histocompatibility complex (MHC) antigens. High metastatic , low immunogenic Lewis lung carcinoma clones (C57BL-H-2(b) origin) ex press low levels of the H-2K(b) MHC antigen. These cells metastasize s pontaneously in C57BL/6J mice. Transfection of syngeneic or allogeneic H-2K genes converted such cells to the nonmetastatic state, but did n ot prevent the growth of the local tumors. Transfection of two H-2K ge nes, syngeneic and allogeneic, into the highly metastatic clone D122, resulted in reduction of the growth rates of the transfectants and pro tected the mice from D122 metastases. In contrast, cells transfected w ith a single class I gene (syngeneic or allogeneic) gave partial prote ction, or did not protect the mice at all from D122 metastases. The co mbination of syngeneic and allogeneic genes in the same tumor cell ele vated the immunogenic properties of the expressing cells and potentiat ed the immune response as was demonstrated by in vitro cytotoxicity an alysis and by limiting dilution cytotoxicity analysis. Increased immun ogenicity by double transfection may constitute an effective therapeut ic modality.