Conversion of Tumors into Autologous Vaccines by Intratumoral Injection of α-Gal Glycolipids that Induce Anti-Galα-Gal Epitope Interaction

الملخص EN

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 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 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.