LIPOFECTION INDIRECTLY INCREASES EXPRESSION OF ENDOGENOUS MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I MOLECULES ON TUMOR-CELLS

Direct intratumoral injection of a lipid/DNA complex encoding an allog eneic major histocompatability complex (MHC) class I molecule leads to regression of both an immunogenic murine tumor and also melanoma lesi ons in some patients. We have sought to understand the mechanism(s) fo r this augmentation of antitumor activity. While optimizing parameters for in vitro gene transfer into the D5 subclone of B16BL6, it was not ed that lipofected tumors not only expressed the new alloantigen but a lso exhibited increased expression of endogenous MHC class I, both H-2 K-b and H-2 D-b. This increase in expression was not restricted to th e small percentage of cells that expressed the transfected gene, but a ppeared to affect the majority of cells in culture. Class I expression was not increased by lipopolysaccharide, DNA alone, lipid, or lipid/l ipopolysaccharide mixtures. Enhanced class I expression required a DNA /lipid complex and was greatest when parameters optimized for gene tra nsfer of the alloantigen were used. All DNA plasmids tested had this e ffect, including one plasmid whose DNA was not transcribed because it lacked an expression cassette. Because of the critical role that MHC c lass I antigens play in immune recognition, we propose that lipid comp lex-mediated gene transfer may provide immunological advantages beyond those that are attributable to expression of the specific gene transf erred.