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.