Developments in CRM197 Glycoconjugates for Anticancer Vaccines | Biomedgrid

Glycoconjugate vaccines that utilize cross reactive material 197 (CRM197) as an immunogenic carrier have shown clinical success against bacterial pathogens such as Haemophilus influenzae type b (Hib), Streptococcus pneumoniae, and Neisseria meningitidis. However, the translation of glycoconjugate vaccine strategies towards cancer has had limited clinical success. Preclinical efforts focused on tumor associated carbohydrate antigen (TACA)-CRM197 conjugates include the Globo H, RM2, Thomsen-nouveau (Tn), Thomsen-Friedenreich (TF), and sialylated Thomsen-nouveau (STn) antigens. These collective efforts have shown robust conjugation chemistry and efficacious immune responses. The immune response towards these CRM197 conjugates produced Gaussian-like distributions as a function of dose, with a maximum response at dosages in the low to medium range. This phenomenon suggests a tolerogenic effect toward the CRM197 immunogen at high doses. An approach to resolve immune tolerance in cancer based glycoconjugate vaccines may be concomitant administration of TACA conjugates. As described by clinical research, the effects of simultaneous administration of antibacterial glycoconjugate vaccines have profound effects on immunological outcome.