alpha-Gal
glycolipids capable of converting
tumors into endogenous
vaccines, have alpha-gal
epitopes (Gal alpha 1-3 Gal beta 1-4GlcNAc-R) and are extracted from rabbit RBC membranes. alpha-Gal
epitopes bind anti-Gal, the most abundant natural antibody in humans constituting 1% of
immunoglobulins. alpha-Gal
glycolipids insert into
tumor cell membranes, bind anti-Gal and activate
complement. The
complement cleavage
peptides C5a and C3a recruit inflammatory cells and APC into the treated lesion. Anti-Gal further opsonizes the
tumor cells and targets them for effective uptake by recruited APC, via
Fc gamma receptors. These APC transport internalized
tumor cells to draining lymph nodes, and present immunogenic
tumor antigen peptides for activation of
tumor specific T cells. The present study demonstrates the ability of alpha-gal
glycolipids treatment to prevent development of
metastases at distant sites and to protect against
tumor challenge in the treated mice. Adoptive transfer studies indicate that this protective immune response is mediated by CD8+ T cells, activated by
tumor lesions turned
vaccine. This T cell activation is potent enough to overcome the suppressive activity of Treg cells present in
tumor bearing mice, however it does not elicit an autoimmune response against
antigens on normal cells. Insertion of alpha-gal
glycolipids and subsequent binding of anti-Gal are further demonstrated with human
melanoma cells, suggesting that intratumoral injection of alpha-gal
glycolipids is likely to elicit a protective immune response against
micrometastases also in
cancer patients.