Autologous
melanoma associated
antigens (MAA) on murine
melanoma cells can elicit a protective anti-
tumor immune response following a variety of
vaccine strategies. Most require effective uptake by antigen presenting cells (APC). APC transport and process internalized MAA for activation of anti-
tumor T cells. One potential problem with clinical
melanoma vaccines against autologous
tumors may be that often
tumor cells do not express surface markers that label them for uptake by APC. Effective uptake of
melanoma cells by APC might be achieved by exploiting the natural anti-Gal antibody which constitutes ~1% of
immunoglobulins in humans. This approach has been developed in a syngeneic mouse model using mice capable of producing anti-Gal. Anti-Gal binds specifically to α-gal
epitopes (Galα1-3Galβ1-4GlcNAc-R). Injection of
glycolipids carrying α-gal
epitopes (α-gal
glycolipids) into
melanoma lesions results in
glycolipid insertion into
melanoma cell membranes, expression of α-gal
epitopes on the
tumor cells and binding of anti-Gal to these
epitopes. Interaction between the Fc portions of bound anti-Gal and Fcγ receptors on APC induces effective uptake of
tumor cells by APC. The resulting anti-MAA immune response can be potent enough to destroy distant
micrometastases. A clinical trial is now open testing effects of intratumoral α-gal
glycolipid injections in
melanoma patients.