We have investigated the synthesis of various microbial components that activate or modulate immune responses via innate immune receptors. Here, we report on the application of their immunomodulatory effects to the developments of immune adjuvants and cancer vaccines.Self-adjuvanting vaccines consisting in antigens and adjuvants have been investigated to improve vaccine efficacy and safety. We synthesized self-adjuvanting cancer vaccines composed of a trimeric tumor-associated carbohydrate antigen Sialyl-Tn (STn), a TLR2 agonist Pam3CSK4 as an adjuvant, and a T-helper epitope, since clustered STn antigens are highly expressed on many cancer cells. Immunization of vaccines in mice induced the anti-triSTn IgG antibodies, which recognized triSTn-expressing cell lines PANC-1 and HepG2.
Humans do not have α-gal epitope but have natural antibodies (Ab) against α-gal. The reaction of anti-Gal Abs with α-gal causes hyperacute rejection in xenogeneic organ transplantation. In this study, we applied the ADC (antibody-drug conjugate) concept to develop a novel α-gal-based tumor immunotherapy.The α-gal trisaccharide was efficiently synthesized by one-pot or one-flow glycosylation procedures. After chemical synthesis of α-gal, we achieved concise chemical conjugation of antibodies with α-gal. The α-gal-Ab conjugates showed increased complement dependent cytotoxicity (CDC) by recruiting natural Abs through the interaction between α-gal and anti-Gal Abs. Utilization of α-gal dendrimer allowed introduction of large amounts of α-gal epitope to the antibody. The conjugated antibodies with α-gal dendrimer showed potent CDC without loss of affinity for the target cell. The method described here will enable re-development of antibodies to improve their potency.