title: Conversion of tumors into autologous vaccines by intratumoral injection of α-Gal glycolipids that induce anti-Gal/α-Gal epitope interaction.
abstract: Anti-Gal is the most abundant antibody in humans, constituting 1% of immunoglobulins. Anti-Gal binds specifically α-gal epitopes (Galα1-3Galβ1-4GlcNAc-R). Immunogenicity of autologous tumor associated antigens (TAA) is greatly increased by manipulating tumor cells to express α-gal epitopes and bind anti-Gal. Glycolipids with αgal epitopes (α-gal glycolipids) injected into tumors insert into the tumor cell membrane. Anti-Gal binding to the multiple α-gal epitopes de novo presented on the tumor cells results in targeting of these cells to APC via the interaction between the Fc portion of the bound anti-Gal and Fcγ; receptors on APC. The APC process and present immunogenic TAA peptides and thus, effectively activate tumor specific CD4+ helper T cells and CD8+ cytotoxic T cells which destroy tumor cells in micrometastases. The induced immune response is potent enough to overcome immunosuppression by Treg cells. A phase I clinical trial indicated that α-gal glycolipid treatment has no adverse effects. In addition to achieving destruction of micrometastases in cancer patients with advance disease, α-gal glycolipid treatment may be effective as neo-adjuvant immunotherapy. Injection of α-gal glycolipids into primary tumors few weeks prior to resection can induce a protective immune response capable of destroying micrometastases expressing autologous TAA, long after primary tumor resection.
authors.affiliation: Department of Surgery, University of Massachusetts Medical School, Worcester, MA 01655, USA. uri.galili@umassmed.edu
authors.forename: Uri
authors.initials: U
authors.lastname: Galili
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000008:administration & dosage* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D002240:Carbohydrate Sequence; D006017:Glycolipids / Q000008:administration & dosage* / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D015552:Injections, Intralesional; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D018345:Mice, Knockout; D061206:Neoplasm Micrometastasis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014312:Trisaccharides / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000912:Antibodies, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D006017:Glycolipids; D014312:Trisaccharides; C076569:alpha-galactosyl epitope