VACCINIA VIRUS MUC1 IMMUNIZATION OF MICE - IMMUNE-RESPONSE AND PROTECTION AGAINST THE GROWTH OF MURINE TUMORS BEARING THE MUC1 ANTIGEN

MUC1 is a mucin found on the apical surfaces of some normal mammalian mucin-secreting cells. It is characterized by heavy glycosylation and a 20-amino-acid tandem repeat segment. In most cases of human breast a denocarcinoma, this antigen is overexpressed. Moreover, abnormal glyco sylation exposes a novel peptide epitope within the tandem repeat, suc h that antibodies to this epitope can distinguish normal from malignan t adenocarcinomatous breast tissue. We have constructed a vaccinia vir us (VV) that carries the cDNA for the MUC1 antigen. Murine and human c ells infected with this virus express the MUC1 molecule, with three to four tandem repeats per molecule and with the tumor-associated epitop es exposed. Mice immunized with this virus produce antibodies that rec ognize MUC1 outside the tandem repeat, within the tandem repeat, and w ithin the tumor-associated protein core epitope. Tumorogenic P815 (DBA ) and 3T3 (BALB/c) cells have been transfected with MUC1. Thirty perce nt of DBA mice immunized with VV-MUC1 are protected from growth of P81 5-MUC1 tumors when implanted with 10(5) cells. Immunized BALB/c mice s how a late development of transfected 3T3 tumor cells. Immunized mice show a moderate MUC1-specific IgG titer, but it cannot be correlated w ith subsequent tumor rejection. No evidence for a MUC1-specific cytoto xic T lymphocyte response has been found after immunization with VV-MU C1.