REVERSAL OF TOLERANCE TO HUMAN MUC1 ANTIGEN IN MUC1 TRANSGENIC MICE IMMUNIZED WITH FUSIONS OF DENDRITIC AND CARCINOMA-CELLS

Immunological unresponsiveness established by the elimination or anerg y of self-reactive lymphocyte clones is of importance to immunization against tumor-associated antigens, In this study, we have investigated induction of immunity against the human MUC1 carcinoma-associated ant igen in MUC1 transgenic mice unresponsive to MUC1 antigen. Immunizatio n of adult MUC1 transgenic mice with irradiated MUC1-positive tumor ce lls was unsuccessful in reversing unresponsiveness to MUC1, By contras t, fusions of dendritic cells with MUC1-positive tumor cells induced c ellular and humoral immunity against MUC1. Immunization with the dendr itic cell fusions that express MUC1 resulted in the rejection of estab lished metastases and no apparent autoimmunity against normal tissues. These findings demonstrate that unresponsiveness to the MUC1 tumor-as sociated antigen is reversible by immunization with heterokaryons of d endritic cells and MUC1-positive carcinoma cells.