Synthesis of alpha-galactosyl epitopes by recombinant alpha1,3galactosyl transferase for opsonization of human tumor cell vaccines by anti-galactose.

Abstract

The immunogenicity of tumor-associated antigens in autologous tumor vaccines is limited because of insufficient uptake by antigen-presenting cells (APC). Anti-Galactose (Gal) IgG, abundantly produced in humans, can serve as a natural adjuvant increasing the uptake of vaccinating autologous tumor cell membranes by APC. Anti-Gal interacts with the alpha-galactosyl epitope (Ga1alpha1-3Galbeta1-4GlcNAc-R), which is normally absent in humans. This epitope is produced in large amounts in nonprimate mammals and New World monkeys due to the intracellular activity of the glycosylation enzyme alphal,3galactosyltransferase. alpha-Galactosyl epitopes were synthesized in vitro on human tumor cells by soluble recombinant alphal,3galactosyltransferase. Anti-Gal binding to these epitopes induces the effective uptake of the tumor cells by APC with Fc receptors that interact with the Fc portion of this natural antibody. It is suggested that synthesis of alpha-galactosyl epitopes on freshly isolated human tumor cell membranes, followed by their administration back to the patient, will result in the in situ opsonization of the membranes by anti-Gal, thereby improving the uptake, processing, and presentation of autologous tumor-associated antigens by APC with Fc receptors.