Carbohydrate antigen delivery by water soluble copolymers as potential anti-cancer vaccines

Abstract

Tumor associated carbohydrate antigens (TACAs) are overexpressed on tumor cells, which renders them attractive targets for anti-cancer vaccines. To overcome the poor immunogenicity of TACAs, we designed a polymer platform for antigen presentation by co-delivering TACA and helper T (Th) cell epitope on the same chain. The block copolymer was synthesized by cyanoxyl-mediated free radical polymerization followed by conjugation with a TACA Tn antigen and a mouse Th-cell peptide epitope derived from polio virus (PV) to afford the vaccine construct. The glycopolymer vaccine elicited an anti-Tn immune response with significant titers of IgG antibodies, which recognized Tn-expressing tumor cells.

Valency and density matter: Deciphering impacts of immunogen structures on immune responses against a tumor associated carbohydrate antigen using synthetic glycopolymers

“…In summary, while glycopolymers have been applied in immunization studies, 53–56 this is the first time a series of synthetic glycopolymers with defined length and number of carbohydrate antigen Tn have been utilized to decipher the codes of antigen valency and density on T cell independent B cell activation. With the 450 kDa polymer, bell shaped ASC responses were found depending on the number of antigen per chain.…”

Glycopolymeric Materials for Advanced Applications

“…Very recently, a block glycopolymer has been prepared by cyanoxyl-mediated free radical polymerization followed by conjugation with a tumor associated carbohydrate antigens (TACA) Tn antigen and a mouse T helper cells (Th cells) peptide epitope derived from polio virus to afford the vaccine construct ( Figure 10 ) [ 61 ].…”

Recent advances in carbohydrate-based cancer vaccines

“…Thus, while carbohydrate antigens are potentially suited for immune recognition and killing, their use in cancer vaccines has remained challenging due to the difficulties associated with overcoming immunotolerance and immunosuppression. Carbohydrate antigens are devoid of the inherent immunogenicity of bacterial antigens and techniques to improve their immunological recognition, including defining the appropriate TACA, chemically modifying the antigens, and increasing immunological reactivity, are being investigated (Hutchins et al 2017;Qin et al 2014). To date, the gains have been modest, primarily due to immune escape produced by the selection of tumor cells lacking carbohydrate-based immunogenic antigens.…”