Murine immune response to cells transfected with human MUC1: immunization with cellular and synthetic antigens.
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.
Apostolopoulos
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Austin Research Institute, Heidelberg, Victoria, Australia.
Xing
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PX
McKenzie
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D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D000912:Antibodies, Neoplasm / Q000032:analysis; D000951:Antigens, Neoplasm / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed; D007114:Immunization; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D018396:Mucin-1; D009077:Mucins / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D008562:Membrane Glycoproteins; D018396:Mucin-1; D009077:Mucins; D011993:Recombinant Fusion Proteins