Figure 1.

TMG glycomimetic vaccine mechanisms of immune activation. After systemic delivery of the vaccine antigens, (1) there is a rapid expansion of γδ T cells. It is unknown whether γδ TCRs expand by binding directly to the vaccine glycomimetic product, or whether the antigen is presented by DCs. Expansion of γδ T cells is independent of whether mice bear tumors expressing TMGs, so while the vaccine may also block the immune-suppressive action of TMGs upon T cells this mechanism is unlikely to account for the initial expansion. (2) In mice bearing TMG-expressing tumors, vaccination affords a significant increase in γδ T cells TILs. (3) The effector activity generates secondary antigens or neoantigens. (4) Putative neoantigens (not yet identified) circulate and are presented to CD8+ αβ T cells which (5, 6) expand as a second wave mainly comprising CD8+ T cells that also become TILs. The generation of in vivo T-cell memory in glycomimetic vaccines was not evaluated. However, anti-TMG humoral immunity (evaluated as a surrogate marker) matures and class-switches from IgM to IgG.