Department of Surgery
Adjuvants, Immunologic; Animals; Antibodies, Neoplasm; Antigen-Presenting Cells; Antigens, Tumor-Associated, Carbohydrate; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cancer Vaccines; Carbohydrate Sequence; Glycolipids; Humans; Immunotherapy; Injections, Intralesional; Melanoma, Experimental; Mice; Mice, Knockout; Neoplasm Micrometastasis; T-Lymphocytes, Regulatory; Trisaccharides
Immunology and Infectious Disease
Anti-Gal is the most abundant antibody in humans, constituting 1% of immunoglobulins. Anti-Gal binds specifically alpha-gal epitopes (Galalpha1-3Galbeta1-4GlcNAc-R). Immunogenicity of autologous tumor associated antigens (TAA) is greatly increased by manipulating tumor cells to express alpha-gal epitopes and bind anti-Gal. Glycolipids with alphagal epitopes (alpha-gal glycolipids) injected into tumors insert into the tumor cell membrane. Anti-Gal binding to the multiple alpha-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 Fcgamma; 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 alpha-gal glycolipid treatment has no adverse effects. In addition to achieving destruction of micrometastases in cancer patients with advance disease, alpha-gal glycolipid treatment may be effective as neo-adjuvant immunotherapy. Injection of alpha-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.
Clinical and developmental immunology
Galili, Uri, "Conversion of tumors into autologous vaccines by intratumoral injection of alpha-Gal glycolipids that induce anti-Gal/alpha-Gal epitope interaction" (2011). Open Access Articles. 2397.