title: MUC1 Vaccines, Comprised of Glycosylated or Non-Glycosylated Peptides or Tumor-Derived MUC1, Can Circumvent Immunoediting to Control Tumor Growth in MUC1 Transgenic Mice.
abstract: It remains challenging to produce decisive vaccines against MUC1, a tumor-associated antigen widely expressed by pancreas, breast and other tumors. Employing clinically relevant mouse models, we ruled out such causes as irreversible T-cell tolerance, inadequate avidity, and failure of T-cells to recognize aberrantly glycosylated tumor MUC1. Instead, every tested MUC1 preparation, even non-glycosylated synthetic 9mer peptides, induced interferon gamma-producing CD4(+) and CD8(+) T-cells that recognized glycosylated variants including tumor-associated MUC1. Vaccination with synthetic peptides conferred protection as long as vaccination was repeated post tumor challenge. Failure to revaccinate post challenge was associated with down-regulated tumor MUC1 and MHC molecules. Surprisingly, direct admixture of MUC1-expressing tumor with MUC1-hyperimmune T-cells could not prevent tumor outgrowth or MUC1 immunoediting, whereas ex vivo activation of the hyperimmune T-cells prior to tumor admixture rendered them curative. Therefore, surrogate T-cell preactivation outside the tumor bed, either in culture or by repetitive vaccination, can overcome tumor escape.
authors.affiliation: Department of Immunology, Mayo Clinic in Arizona, Scottsdale, AZ, United States of America.
authors.forename: Vani
authors.initials: V
authors.lastname: Lakshminarayanan
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia, Athens, GA, United States of America.
authors.forename: Nitin T
authors.initials: NT
authors.lastname: Supekar
authors.affiliation: Department of Immunology, Mayo Clinic in Arizona, Scottsdale, AZ, United States of America.
authors.forename: Jie
authors.initials: J
authors.lastname: Wei
authors.affiliation: Hematology/Oncology, Mayo Clinic in Arizona, Scottsdale, AZ, United States of America.
authors.forename: Dustin B
authors.initials: DB
authors.lastname: McCurry
authors.affiliation: Biostatistics, Mayo Clinic in Arizona, Scottsdale, AZ, United States of America.
authors.forename: Amylou C
authors.initials: AC
authors.lastname: Dueck
authors.affiliation: Biostatistics, Mayo Clinic in Arizona, Scottsdale, AZ, United States of America.
authors.forename: Heidi E
authors.initials: HE
authors.lastname: Kosiorek
authors.affiliation: Department of Immunology, Mayo Clinic in Arizona, Scottsdale, AZ, United States of America.
authors.forename: Priyanka P
authors.initials: PP
authors.lastname: Trivedi
authors.affiliation: Department of Immunology, Mayo Clinic in Arizona, Scottsdale, AZ, United States of America.
authors.forename: Judy M
authors.initials: JM
authors.lastname: Bradley
authors.affiliation: Department of Immunology, Mayo Clinic in Arizona, Scottsdale, AZ, United States of America.
authors.forename: Cathy S
authors.initials: CS
authors.lastname: Madsen
authors.affiliation: Department of Immunology, Mayo Clinic in Arizona, Scottsdale, AZ, United States of America.
authors.forename: Latha B
authors.initials: LB
authors.lastname: Pathangey
authors.affiliation: Department of Immunology, Mayo Clinic in Arizona, Scottsdale, AZ, United States of America.
authors.forename: Dominique B
authors.initials: DB
authors.lastname: Hoelzinger
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia, Athens, GA, United States of America.
authors.forename: Margreet A
authors.initials: MA
authors.lastname: Wolfert
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia, Athens, GA, United States of America.
authors.forename: Geert-Jan
authors.initials: GJ
authors.lastname: Boons
authors.affiliation: Department of Immunology, Mayo Clinic in Arizona, Scottsdale, AZ, United States of America.|Hematology/Oncology, Mayo Clinic in Arizona, Scottsdale, AZ, United States of America.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Cohen
authors.affiliation: Department of Immunology, Mayo Clinic in Arizona, Scottsdale, AZ, United States of America.|Department of Biochemistry/Molecular Biology, Mayo Clinic in Arizona, Scottsdale, AZ, United States of America.|Hematology/Oncology, Mayo Clinic in Arizona, Scottsdale, AZ, United States of America.
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Gendler
mesh_terms: D000818:Animals; D000941:Antigens / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D006031:Glycosylation; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018396:Mucin-1 / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control*; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019139:Tumor Escape
chemical_list: D000941:Antigens; D019496:Cancer Vaccines; C060192:MUC1 protein, human; D018396:Mucin-1; D010455:Peptides