A bifunctional fusion membrane-based biocompatible nanovaccine to potentiate cancer immunotherapy.

Abstract

Background: Cancer cell membrane-based nanovaccines derived from patients' tumor tissues have shown promising features as a personalized cancer treatment strategy. However, the weak immunogenicity of autologous tumor antigens undermines the therapeutic effects of personalized vaccines. Methods: We synthesized a biomimetic nanovaccine, Bio-HCP@FM-NPs, composed of senescent tumor cell membranes, Escherichia coli cytoplasmic membrane extracts, and granulocyte-macrophage colony-stimulating factor (GM-CSF)-encapsulated biocompatible hypercross-linked polymer nanoparticles. The nanovaccine's antitumor and enhanced immunotherapy effects were demonstrated in multiple tumor models. The tumor prevention effects of nanovaccine were assessed using a postoperative recurrence model. Results: The Bio-FM@HCP-NP vaccine showed promising therapeutic efficacy in the B16-F10 melanoma mouse model and significantly synergized with anti-PD-1 immunotherapy across multiple tumor models. Mechanistically, GM-CSF was promptly released to recruit naïve DCs to the nanovaccine. Thereafter, immature DCs were vigorously activated by FM-NPs, thereby activating the cytotoxic T cells. Furthermore, Bio-HCP@FM-NPs induced robust antigen-specific immune responses, prolonging postoperative survival in mice and providing long-term protection against tumor recurrence. Targeted depletion of immune cell populations revealed that T and B cells were essential for vaccine-induced tumor regression. Conclusion: The Bio-HCP@FM-NPs showed significant promise for immunotherapy and tailored postoperative treatment of cancer, leveraging the strong activation of innate immunity by senescent tumor cell membranes and bacterial cytoplasmic membrane extracts.