Biomaterial Database

Murine immune response to cells transfected with human MUC1: immunization with cellular and synthetic antigens. 1994

V Apostolopoulos, and P X Xing, and I F McKenzie

Austin Research Institute, Heidelberg, Victoria, Australia.

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.

UI	MeSH Term	Description	Entries
D006968	Hypersensitivity, Delayed	An increased reactivity to specific antigens mediated not by antibodies but by sensitized T CELLS.	Hypersensitivity, Tuberculin-Type,Hypersensitivity, Type IV,Tuberculin-Type Hypersensitivity,Type IV Hypersensitivity,Delayed Hypersensitivity,Delayed Hypersensitivities,Hypersensitivity, Tuberculin Type,Tuberculin Type Hypersensitivity,Tuberculin-Type Hypersensitivities,Type IV Hypersensitivities
D007114	Immunization	Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).	Immunologic Stimulation,Immunostimulation,Sensitization, Immunologic,Variolation,Immunologic Sensitization,Immunological Stimulation,Sensitization, Immunological,Stimulation, Immunologic,Immunizations,Immunological Sensitization,Immunological Sensitizations,Immunological Stimulations,Sensitizations, Immunological,Stimulation, Immunological,Stimulations, Immunological,Variolations
D008562	Membrane Glycoproteins	Glycoproteins found on the membrane or surface of cells.	Cell Surface Glycoproteins,Surface Glycoproteins,Cell Surface Glycoprotein,Membrane Glycoprotein,Surface Glycoprotein,Glycoprotein, Cell Surface,Glycoprotein, Membrane,Glycoprotein, Surface,Glycoproteins, Cell Surface,Glycoproteins, Membrane,Glycoproteins, Surface,Surface Glycoprotein, Cell,Surface Glycoproteins, Cell
D008807	Mice, Inbred BALB C	An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research.	BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009077	Mucins	High molecular weight mucoproteins that protect the surface of EPITHELIAL CELLS by providing a barrier to particulate matter and microorganisms. Membrane-anchored mucins may have additional roles concerned with protein interactions at the cell surface.	Mucin
D011993	Recombinant Fusion Proteins	Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.	Fusion Proteins, Recombinant,Recombinant Chimeric Protein,Recombinant Fusion Protein,Recombinant Hybrid Protein,Chimeric Proteins, Recombinant,Hybrid Proteins, Recombinant,Recombinant Chimeric Proteins,Recombinant Hybrid Proteins,Chimeric Protein, Recombinant,Fusion Protein, Recombinant,Hybrid Protein, Recombinant,Protein, Recombinant Chimeric,Protein, Recombinant Fusion,Protein, Recombinant Hybrid,Proteins, Recombinant Chimeric,Proteins, Recombinant Fusion,Proteins, Recombinant Hybrid
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein