Conversion of tumors into autologous vaccines by intratumoral injection of ?-Gal glycolipids that induce anti-Gal/?-Gal epitope interaction.
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ABSTRACT: Anti-Gal is the most abundant antibody in humans, constituting 1% of immunoglobulins. Anti-Gal binds specifically ?-gal epitopes (Gal?1-3Gal?1-4GlcNAc-R). Immunogenicity of autologous tumor associated antigens (TAA) is greatly increased by manipulating tumor cells to express ?-gal epitopes and bind anti-Gal. Glycolipids with ?gal epitopes (?-gal glycolipids) injected into tumors insert into the tumor cell membrane. Anti-Gal binding to the multiple ?-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 Fc?; 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 ?-gal glycolipid treatment has no adverse effects. In addition to achieving destruction of micrometastases in cancer patients with advance disease, ?-gal glycolipid treatment may be effective as neo-adjuvant immunotherapy. Injection of ?-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.
SUBMITTER: Galili U
PROVIDER: S-EPMC3226304 | biostudies-literature | 2011
REPOSITORIES: biostudies-literature
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