Chemoenzymatic Synthesis of 9NHAc‐GD2 Antigen to Overcome the Hydrolytic Instability of O‐Acetylated‐GD2 for Anticancer Conjugate Vaccine Development

Abstract

Ganglioside GD2 is an attractive tumor-associated carbohydrate antigen for anti-cancer vaccine development. However,i ts lowi mmunogenicity and the significant side effects observed with anti-GD2 antibodies present significant obstacles for vaccines.T oo vercome these,anew GD2 derivative bearing an N-acetamide (NHAc) at its non-reducing end neuraminic acid (9NHAc-GD2) has been designed to mimic the 9-O-acetylated-GD2 (9OAc-GD2), aG D2 based antigen with ar estricted expression on tumor cells.9 NHAc-GD2 was synthesized efficiently via achemoenzymatic method and subsequently conjugated with ap owerfulc arrier bacteriophage Qb.M ouse immunization with the Qb-9NHAc-GD2 conjugate elicited strong and long-lasting IgG antibodies, which were highly selective toward9 NHAc-GD2 with little cross-recognition of GD2. Immunization of canines with Qb-9NHAc-GD2 showed the construct was immunogenic in canines with little adverse effects,p aving the wayf or future clinical translation to humans.

Virus-like Particle Display of Vibrio cholerae O-Specific Polysaccharide as a Potential Vaccine against Cholera

“…The 1440 copies per capsid are one of the highest ligand loading levels on Qβ reported to date. 18,19,26,27 MS sequencing of Qβ conjugated with lactoside 3 indicated high functionalization efficiency (80−100%) of lysines (K14, K17, K61, K64, and K68) on the capsid surface and moderate efficiency (46%) of the lysine K3 that lays between monomers in the capsid compared to almost no functionalization (∼1%) of K47, the S1).…”

New opportunities for immunomodulation of the tumour microenvironment using chemical tools

“…2a1). [35][36][37] Abnormal expression or neo-expression of glycans on the surface of tumour cells in various cancer types provides promising epitopes for vaccine development. 38,39 Accordingly, glycopeptides have the potential for wide application in tumour therapy.…”

Canine Melanoma Immunology and Immunotherapy: Relevance of Translational Research

“…Considering the translational relevance of GD2 and GD3 antigens for both canine and human melanomas, relevant veterinary studies of vaccination against these targets suggested their safety and ability to protect canine melanoma patients when provided as an adjunct to conventional therapies (86,88). Nevertheless, adjuvants and/or antigen modifications are needed to increase the immunogenicity of the vaccine to be successfully translated in a standard of care (88,89).…”