MAJOR HISTOCOMPATIBILITY COMPLEX CLASS II-TRANSFECTED TUMOR-CELLS PRESENT ENDOGENOUS ANTIGEN AND ARE POTENT INDUCERS OF TUMOR-SPECIFIC IMMUNITY

We have developed an immunotherapy in which tumor cells transfected wi th syngeneic major histocompatibility complex (MHC) class II genes are cell-based vaccines for the treatment of established tumor and metast atic disease, If this strategy is to be used clinically, convenient me thods for generating class II+ turner cells are necessary, Interferon- gamma treatment or transduction of the class LI transactivator (CIITA) gene induces class IE expression but also up-regulates the class II-a ssociated accessory molecules, invariant chain (Ii) and DM, To determi ne if interferon-gamma treatment and CIITA transduction are potential immunotherapies, we assessed the tumorigenicity of sarcoma cells expre ssing combinations of class II, Ii, and DM. Since we hypothesized that class IT-transfected tumor cells not coexpressing Ii and DM present e ndogenously encoded tumor peptides, we have assessed the transfectants for antigen presentation activity to MHC class II-restricted antigen- specific CD4(+) T cells, Tumor challenge studies demonstrate that tumo r cells expressing class II without coexpression of Ii or Ii plus DM a re highly immunogenic and preferentially present endogenous antigens, while tumors coexpressing class II with Ii or Ii plus DM are not effec tive Immunogens, Because tumor rejection correlates with expression of class II without coexpression of Ii and DM, tile most efficacious vac cines will express MHC class II without coexpression of Ii and DM and will preferentially present endogenous antigen.