MHC CLASS II-TRANSFECTED TUMOR-CELLS DIRECTLY PRESENT ANTIGEN TO TUMOR-SPECIFIC CD4(-LYMPHOCYTES() T)

We have developed and shown to be efficacious an immunotherapeutic str ategy to enhance the generation of tumor-specific CD4(+) T helper lymp hocytes. The approach uses autologous tumor cells genetically modified to express syngeneic MHC class II genes as cell-based immunogens and is based on the hypothesis that tumor cells directly present tumor Ags to CD4(+) T cells. Since the conventional pathway for CD4(+) T cell a ctivation is indirect via professional APC, induction of immunity foll owing immunization with class Il-transfected tumor cells was examined in bone marrow chimeric mice. Both tumor and host-derived cells are AP C for tumor Ags, suggesting that the efficacy of tumor cell vaccines c an be significantly improved by genetic modifications that enhance tum or cell Ag presentation.