title: Cancer immunotherapy for pancreatic cancer utilizing α-gal epitope/natural anti-Gal antibody reaction.
abstract: Pancreatic ductal adenocarcinoma (PDAC) has the poorest prognosis of all malignancies and is largely resistant to standard therapy. Novel treatments against PDAC are desperately needed. Anti-Gal is the most abundant natural antibody in humans, comprising about 1% of immunoglobulins and is also naturally produced in apes and Old World monkeys. The anti-Gal ligand is a carbohydrate antigen called "α-gal epitopes" with the structure Galα1-3Galβ1-4GlcNAc-R. These epitopes are expressed as major carbohydrate antigens in non-primate mammals, prosimians, and New World monkeys. Anti-Gal is exploited in cancer vaccines to increase the immunogenicity of antigen-presenting cells (APCs). Cancer cells or PDAC tumor lysates are processed to express α-gal epitopes. Vaccination with these components results in in vivo opsonization by anti-Gal IgG in PDAC patients. The Fc portion of the vaccine-bound anti-Gal interacts with Fcγ receptors of APCs, inducing uptake of the vaccine components, transport of the vaccine tumor membranes to draining lymph nodes, and processing and presentation of tumor-associated antigens (TAAs). Cancer vaccines expressing α-gal epitopes elicit strong antibody production against multiple TAAs contained in PDAC cells and induce activation of multiple tumor-specific T cells. Here, we review new areas of clinical importance related to the α-gal epitope/anti-Gal antibody reaction and the advantages in immunotherapy against PDAC.
authors.affiliation: Masahiro Tanemura, Hiroki Akamatsu, Department of Surgery, Osaka Police Hospital, 10-31 Kitayamacho Tennoujiku, Osaka 543-0035, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tanemura
authors.affiliation: Masahiro Tanemura, Hiroki Akamatsu, Department of Surgery, Osaka Police Hospital, 10-31 Kitayamacho Tennoujiku, Osaka 543-0035, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Miyoshi
authors.affiliation: Masahiro Tanemura, Hiroki Akamatsu, Department of Surgery, Osaka Police Hospital, 10-31 Kitayamacho Tennoujiku, Osaka 543-0035, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nagano
authors.affiliation: Masahiro Tanemura, Hiroki Akamatsu, Department of Surgery, Osaka Police Hospital, 10-31 Kitayamacho Tennoujiku, Osaka 543-0035, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Eguchi
authors.affiliation: Masahiro Tanemura, Hiroki Akamatsu, Department of Surgery, Osaka Police Hospital, 10-31 Kitayamacho Tennoujiku, Osaka 543-0035, Japan.
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Matsunami
authors.affiliation: Masahiro Tanemura, Hiroki Akamatsu, Department of Surgery, Osaka Police Hospital, 10-31 Kitayamacho Tennoujiku, Osaka 543-0035, Japan.
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Taniyama
authors.affiliation: Masahiro Tanemura, Hiroki Akamatsu, Department of Surgery, Osaka Police Hospital, 10-31 Kitayamacho Tennoujiku, Osaka 543-0035, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hatanaka
authors.affiliation: Masahiro Tanemura, Hiroki Akamatsu, Department of Surgery, Osaka Police Hospital, 10-31 Kitayamacho Tennoujiku, Osaka 543-0035, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Akamatsu
authors.affiliation: Masahiro Tanemura, Hiroki Akamatsu, Department of Surgery, Osaka Police Hospital, 10-31 Kitayamacho Tennoujiku, Osaka 543-0035, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.affiliation: Masahiro Tanemura, Hiroki Akamatsu, Department of Surgery, Osaka Police Hospital, 10-31 Kitayamacho Tennoujiku, Osaka 543-0035, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000917:Antibody Formation; D000937:Antigen-Antibody Reactions; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D021441:Carcinoma, Pancreatic Ductal / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D000939:Epitopes; D006801:Humans; D008024:Ligands; D014411:Neoplastic Stem Cells / Q000276:immunology / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D014312:Trisaccharides / Q000276:immunology*; D059016:Tumor Microenvironment
chemical_list: D000906:Antibodies; D019496:Cancer Vaccines; D000939:Epitopes; D008024:Ligands; D014312:Trisaccharides; C076569:alpha-galactosyl epitope
keywords: Cancer antigen; Cancer stem cell; Cancer vaccine; Carbohydrate research; Immunotherapy; MUC1; Pancreatic cancer; α-gal epitopes