l-Rhamnose Antigen: A Promising Alternative to α-Gal for Cancer Immunotherapies

Abstract

The targeting of autologous vaccines toward antigen presenting cells (APCs) via the in vivo complexation between anti α-Gal (anti-Gal) antibodies and α-Gal antigens presents a promising cancer immunotherapy with enhanced immunogenicity. This strategy takes advantage of the ubiquitous anti-Gal antibody in human serum. In contrast to the α-Gal epitope, the recent identification of high titers of anti-l-rhamnose (anti-Rha) antibodies in humans reveals a new approach toward immunotherapy employing l-rhamnose (Rha) monosaccharides. In order to evaluate this simple antigen in preclinical applications, we have synthesized Rha-conjugated immunogens and successfully induced high titers of anti-Rha antibodies in wildtype mice. Moreover, our studies demonstrate for the first time that wildtype mice could replace α1,3galactosyltransferase knockout (α1,3GT KO) mice in such antigen/antibody-mediated vaccine design when developing cancer immunotherapies.

Antibody-Recruiting Molecules: An Emerging Paradigm for Engaging Immune Function in Treating Human Disease

“…To this end, modern techniques in rational ligand design,(164) and high-throughput chemistry(165) and biology(166) are likely to prove enabling, and recent strategies for the discovery of novel antibody-binding carbohydrate motifs using array technologies,(167–169) the systematic identification of antibody biomarkers for both healthy and disease states(170) and the identification of compounds capable of modulating protein-protein interactions,(171–174) provide cause for optimism along these lines. Finally, novel chemical scaffolds (e.g., for targeting multiple receptors at once),(71, 72, 74, 175) and assembly strategies (e.g., in vivo bioorthogonal chemistry),(176, 177) have the potential to facilitate ARM optimization.…”

Synthesis of a Liposomal MUC1 Glycopeptide-Based Immunotherapeutic and Evaluation of the Effect of l-Rhamnose Targeting on Cellular Immune Responses

“…Anti-Rha antibodies were among the most abundant in humans and can also be generated in readily available non-transgenic mice. 9, 50, 51 In fact, Rha is now one of the most effective natural antibody eliciting molecules known 52 and Rha has been conjugated to lipids to recruit anti-Rha antibodies to tumor cells. 53, 54 …”

Synthesis of rhamnosylated arginine glycopeptides and determination of the glycosidic linkage in bacterial elongation factor P

“…23 Synthesis of the two rhamnosylated arginine building blocks 1 and 2 began with preparation of the α- and β-configured glycosyl isothiocyanates 3 21 and 4 , both of which were accessed from rhamnosyl acetate 5 24 as a common precursor (Scheme 1A). To access α-isothiocyanate 3 , rhamnosyl chloride 6 25 was treated with KSCN in the presence of catalytic TBAI in refluxing acetonitrile.…”