A lymph node-targeted cell-nanoadjuvant conjugate enhances dendritic cell-T cell crosstalk for cancer immunotherapy

Dendritic cell (DC) vaccines represent a promising immunotherapeutic strategy by eliciting potent anti-tumor immunity. However, their clinical application remains limited due to poor lymph node (LN) targeting and inadequate T cell activation. Here, we developed an LN-targeted cell-nanoadjuvant conjugate by click-chemistry conjugation of anti-PD-1 antibodies ( α PD-1) and Resiquimod (R848) liposomes to DC vaccines (DCVs) (DCV- α PD-1/Lipo) to enhance DC-T cell crosstalk for cancer immunotherapy. DCV- α PD-1/Lipo maintains higher co-stimulatory molecule expression and antigen presentation with enhanced LN targeting efficiency than conventional DC vaccines. The surface-conjugated α PD-1 increases DC-T cell adhesion by 4.97-fold while amplifying the IFN- γ /IL-12 positive feedback loop, thereby potentiating T cell activity and augmenting effector T cells and other immune cells mediated anti-tumor efficacy. This multifunctional integration of adaptive DC therapy, nanoadjuvants and checkpoint blockade establishes an effective approach for next-generation DC therapy. A novel dendritic cell vaccine (DCV- α PD-1/Lipo) was constructed by conjugating α PD-1 and R848-loaded liposomes on DCs, which improved lymph node targeting and DC-T cell crosstalk to promote robust anti-tumor immunity.