A natural IgM hitchhiking strategy for delivery of cancer nanovaccines to splenic marginal zone B cells.

B cell-targeted cancer vaccines are receiving increasing attention in immunotherapy due to the combined antibody-secreting and antigen-presenting functions. In this study, we propose a natural IgM-hitchhiking delivery strategy to co-deliver tumor antigens and adjuvants to splenic marginal zone B (MZB) cells. We constructed nanovaccines (FA-sLip/OVA/MPLA) consisting of classical folic acid (FA)-conjugated liposomes co-loaded with ovalbumin (OVA) and toll-like receptor 4 agonists, MPLA. We found that natural IgM absorption could be manipulated at the bio-nano interface on FA-sLip/OVA/MPLA, enabling targeted delivery to splenic MZB cells. Systemic administration of FA-sLip/OVA/MPLA effectively activated splenic MZB cells via IgM-mediated multiplex pathways, eliciting antigen-specific humoral and cytotoxic T lymphocyte responses, and ultimately retarding E.G7-OVA tumor growth. In addition, combining FA-sLip/OVA/MPLA immunization with anti-PD-1 treatments showed improved antitumor efficiency. Overall, this natural IgM-hitchhiking delivery strategy holds great promise for efficient, splenic MZB cell-targeted delivery of cancer vaccines in future applications. Splenic MZB cells-selective co-delivery of cancer antigens and TLR4 agonists was realized via a natural IgM-hitchhiking delivery strategy. The nanovaccines could capture natural IgM in the circulation and led to the accumulation in splenic MZB cells, eliciting lasting tumor antigen-specific antibodies production and cytotoxic T lymphocyte responses. [Display omitted] • Proposing a natural IgM-hitchhiking delivery strategy to deliver nanovaccines to splenic MZB cells • Utilizing the combined antigen-specific humoral and cellular immune of splenic MZB cells for cancer immunotherapy • Improving antitumor efficiency through combination with nanovaccines and anti-PD-1 treatments [ABSTRACT FROM AUTHOR]