Biomimetic Nanoparticles Enabled by Cascade Cell Membrane Coating for Direct Cross‐Priming of T Cells

Despite the activation of T lymphocytes by antigen‐presenting cells being responsible for eliciting antigen‐specific immune responses, their crosstalking suffers from temporospatial limitations and endogenous influencing factors, which restrict the generation of a strong antitumor immunity. Here, cascade cell membrane coating is reported to prepare biomimetic nanoparticles (BNs) that can manipulate the cross‐priming of T cells. BNs are obtained from coating nanoparticulate substrates with cell membranes extracted from dendritic cells (DCs) that are pre‐pulsed with cancer cell membrane‐coated nanoparticles. With a DC membrane that presents an array of cancer cell membrane antigen epitopes, BNs inherit the intrinsic membrane function of DCs, which can directly cross‐prime T cells and provoke robust yet antigen‐specific antitumor responses in multiple mouse models. Combination with clinical anti‐programmed death‐1 antibodies demonstrates a robust way of BNs to achieve desirable tumor regression and survival rate. This work spotlights the impact of nanoparticles on direct cross‐priming of T cells and supports a unique yet modulate platform for boosting an effective adaptive immunity for immunotherapy. The activation of T lymphocytes by antigen‐presenting cells is responsible for eliciting antigen‐specific immune responses, which plays a critical role in immunotherapy. Here, the manipulation of cross‐priming of T cells using biomimetic nanoparticles enabled by cascade cell membrane coating, which provides a unique yet modulate platform for boosting an effective adaptive immunity for immunotherapy, is described.