title: ImMucin: a novel therapeutic vaccine with promiscuous MHC binding for the treatment of MUC1-expressing tumors.
abstract: An optimal cancer vaccine should be able to induce highly potent, long-lasting, tumor-specific responses in the majority of the cancer patient population. One approach for achieving this is to use synthetic peptide vaccines derived from widely expressed tumor-associated antigens, that promiscuously bind multiple MHC class I and class II alleles. MUC1-SP-L (ImMucin, VXL100) is a 21mer peptide encoding the complete signal peptide domain of MUC1, a tumor-associated antigen expressed by over 90% of solid and non-solid tumors. MUC1-SP-L was predicted in silico to bind various MHC class I and MHC class II alleles, covering the majority of the Caucasian population. PBLs obtained from 13 naïve donors all proliferated, with a Stimulation Index (SI≥2), to the MUC1-SP-L peptide, producing mixed CD4+ and CD8+ responses. Similar results were manifested by MUC1-SP-L in PBLs derived from 9 of 10 cancer patients with MUC1 positive tumors. CD4+ and CD8+ T cell populations exhibited CD45RO memory markers and secreted IFN-gamma and IL-2 following stimulation with MUC1-SP-L. These T cells also exhibited proliferation to the MUC1-SP-L inner 9mer epitopes and cytotoxicity against tumor cell lines expressing MUC1 and a concordant MHC class I allele. Cytotoxicity to MUC1-expressing human and murine tumors was shown also in T cells obtained from HLA-A2 transgenic mice and BALB/c syngeneic mice immunized with the MUC1-SP-L and GM-CSF. In an immunotherapy model, BALB/c mice inoculated with metastatic MUC1 transfected murine DA3 mammary tumor cells, exhibited significantly prolonged survival following vaccination with MUC1-SP-L. Our results indicate superior immunological and anti-tumor properties of MUC1-SP-L compared to previously published MUC1-derived epitopes.
authors.affiliation: Vaxil BioTherapeutics Ltd., 13 Einstein Street, Weizmann Science Park, Nes-Ziona 74036, Israel.
authors.forename: Riva
authors.initials: R
authors.lastname: Kovjazin
authors.forename: Ilan
authors.initials: I
authors.lastname: Volovitz
authors.forename: Yulia
authors.initials: Y
authors.lastname: Kundel
authors.forename: Eli
authors.initials: E
authors.lastname: Rosenbaum
authors.forename: Gal
authors.initials: G
authors.lastname: Medalia
authors.forename: Galit
authors.initials: G
authors.lastname: Horn
authors.forename: Nechama I
authors.initials: NI
authors.lastname: Smorodinsky
authors.forename: Baruch
authors.initials: B
authors.lastname: Brenner
authors.forename: Lior
authors.initials: L
authors.lastname: Carmon
mesh_terms: D000368:Aged; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D005260:Female; D006649:Histocompatibility Antigens / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008875:Middle Aged; D018396:Mucin-1 / Q000096:biosynthesis* / Q000276:immunology*; D009369:Neoplasms / Q000628:therapy*; D011485:Protein Binding; D012376:Rodent Diseases / Q000628:therapy; D016019:Survival Analysis
chemical_list: D019496:Cancer Vaccines; D006649:Histocompatibility Antigens; C060192:MUC1 protein, human; D018396:Mucin-1