conversion of tumors into autologous vaccines by intratumoral injection of -gal glycolipids that induce anti-gal-gal epitope interaction瘤内注射肿瘤转化为自体疫苗的加糖脂,从而诱导anti-gal-gal抗原决定基的相互作用.pdfVIP

Hindawi Publishing Corporation Clinical and Developmental Immunology Volume 2011, Article ID 134020, 10 pages doi:10.1155/2011/134020 Review Article Conversion of Tumors into Autologous Vaccines by Intratumoral Injection of α-Gal Glycolipids that Induce Anti-Gal/α-Gal Epitope Interaction Uri Galili Department of Surgery, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA Correspondence should be addressed to Uri Galili, uri.galili@ Received 13 July 2011; Accepted 5 September 2011 Academic Editor: Trina J. Stewart Copyright © 2011 Uri Galili. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Anti-Gal is the most abundant antibody in humans, constituting 1% of immunoglobulins. Anti-Gal binds specifically α-gal epitopes (Galα1-3Galβ 1-4GlcNAc-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 α-gal 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 a