Optimization, Immunological Evaluation, and Combination Study of Mincle-Dependent Self-Adjuvanted Anti-Tn Cancer Vaccines with an External Adjuvant

Nine Tn-based cancer vaccines were designed and synthesized
using
Mincle agonists as a carrier to elucidate the structure–immunogenicity
relationships of Mincle-dependent vaccines. The Immunological evaluation
showed that the immune response levels were significantly influenced
by the acyl chains of trehalose, coupling site of antigen and carriers,
antigen copy number, and coupling mode of acyl chains and trehalose.
Notably, installing the antigen onto the lipid chains of the carrier
could also effectively improve the immunogenicity. Among them, conjugate 9 showed the highest activity. In the presence of EcMPLA (TLR4
agonist) and aluminum hydroxide (Al), the immunological activity of
conjugate 9 could further be improved and significantly
inhibit tumor growth, prolonging the survival time of tumor-challenged
mice. Survived mice also successfully rejected subsequent tumor attacks
without any additional treatment. This work provides guidance for
developing and applying self-adjuvanted cancer vaccines using Mincle
agonists as both the carrier and “build-in” adjuvant.