Leveraging biomimetic synthesis strategy for next-generation dendritic cell nanovaccines

Abstract

The activation of CD8⁺ cytotoxic T-lymphocytes (CTLs) plays the central role in cancer immunotherapy, which depends on the efficient recognition of peptide-major histocompatibility complex (pMHC) by the T cell receptor (TCR) for the first signal, and B7-CD28 co-stimulating for the second signal. To achieve the potent immune stimulatory effect, a genetically engineered cellular membrane nanovesicles platform that integrates antigen self-presentation and immunosuppression reversal (ASPIRE) for cancer immunotherapy was designed. In preclinical mouse models, ASPIRE could markedly improve antigen delivery to lymphoid organs and generate broad-spectrum T-cell responses that eliminate established tumors. This review highlights that the ASPIRE system represents a novel strategy for personalized cancer immunotherapy.

Keywords

Cancer immunotherapy / extracellular vesicles / bioengineering / nanovaccine

References

[1] Waldman AD,Lenardo MJ.A guide to cancer immunotherapy: from T cell basic science to clinical practice.Nat Rev Immunol2020;20:651-68 PMCID:PMC7238960

[2] Saxena M,Melief CJM.Therapeutic cancer vaccines.Nat Rev Cancer2021;21:360-78

[3] Makkouk A.Cancer immunotherapy and breaking immune tolerance: new approaches to an old challenge.Cancer Res2015;75:5-10 PMCID:PMC4286422

[4] Sabado RL,Bhardwaj N.Dendritic cell-based immunotherapy.Cell Res2017;27:74-95 PMCID:PMC5223236

[5] Sanmamed MF.A paradigm shift in cancer immunotherapy: from enhancement to normalization.Cell2018;175:313-26 PMCID:PMC6538253

[6] Zhang P,Zeng Y.Virus-mimetic nanovesicles as a versatile antigen-delivery system.Proc Natl Acad Sci U S A2015;112:E6129-38 PMCID:PMC4653155

[7] Squadrito ML,Hansen SK.EVIR: chimeric receptors that enhance dendritic cell cross-dressing with tumor antigens.Nat Methods2018;15:183-6 PMCID:PMC5833950

[8] Liu C,Xiang X.A nanovaccine for antigen self-presentation and immunosuppression reversal as a personalized cancer immunotherapy strategy.Nat Nanotechnol2022;17:531-40

[9] Kamphorst AO,Nasti T.Rescue of exhausted CD8 T cells by PD-1-targeted therapies is CD28-dependent.Science2017;355:1423-7 PMCID:PMC5595217

[10] Dagogo-Jack I.Tumour heterogeneity and resistance to cancer therapies.Nat Rev Clin Oncol2018;15:81-94

[11] Zhao X,Nie G.Nanocarriers based on bacterial membrane materials for cancer vaccine delivery.Nat Protoc2022;

[12] Ma L,Peng Z.Immunotherapy and prevention of cancer by nanovaccines loaded with whole-cell components of tumor tissues or cells.Adv Mater2021;33:e2104849