Murine immune response to cells transfected with human MUC1: immunization with cellular and synthetic antigens

Abstract

Humans with breast cancer have T-cells in their lymph nodes which recognize a peptide sequence within the variable number of tandem repeats of the mammary mucin, MUC1, which is overexpressed in breast cancer. To find means of making this recognition event into a potent immune response to breast cancer, we used a murine tumor model and have examined the parameters of the immune response to human mucin (MUC1) expressed in murine BALB/c 3T3 cells. We then sought to boost this response with MUC1-containing synthetic peptides, fusion proteins, and natural mucin (HMFG). MUC1+3T3 cells were found to be rejected by BALB/c mice by day 15 due to a cellular [CD3+, Ly2+ (CD8+)] response. The cellular rejection response was accompanied by the generation of CD8+ cytotoxic T-cells, CD4+ delayed-type hypersensitivity, and little anti-MUC1 antibody. This immune response is presumably of the TH1 type (which occurs in CD8 as well as CD4 cells) of CD8+ cytotoxic cells. By contrast, mice immunized with the MUC1 synthetic peptide, a fusion protein, or HMFG have good antibody responses, a delayed-type hypersensitivity reaction, but no cytotoxic T-cells and less tumor protection, possibly a TH2 type response. We conclude that CD8+ cytotoxic anti-mucin cells can produce significant antitumor responses in vivo to a human "tumor" antigen expressed in murine cells; immunization with soluble synthetic or native materials leads to the "humoral" (TH2) type of immunity, and efforts need to be made to convert this to a TH1-type response.