Self-adjuvanting cancer nanovaccines

Abstract

Nanovaccines, a new generation of vaccines that use nanoparticles as carriers and/or adjuvants, have been widely used in the prevention and treatment of various diseases, including cancer. Nanovaccines have sparked considerable interest in cancer therapy due to a variety of advantages, including improved access to lymph nodes (LN), optimal packing and presentation of antigens, and induction of a persistent anti-tumor immune response. As a delivery system for cancer vaccines, various types of nanoparticles have been designed to facilitate the delivery of antigens and adjuvants to lymphoid organs and antigen-presenting cells (APCs). Particularly, some types of nanoparticles are able to confer an immune-enhancing capability and can themselves be utilized for adjuvant-like effect for vaccines, suggesting a direction for a better use of nanomaterials and the optimization of cancer vaccines. However, this role of nanoparticles in vaccines has not been well studied. To further elucidate the role of self-adjuvanting nanovaccines in cancer therapy, we review the mechanisms of antitumor vaccine adjuvants with respect to nanovaccines with self-adjuvanting properties, including enhancing cross-presentation, targeting signaling pathways, biomimicking of the natural invasion process of pathogens, and further unknown mechanisms. We surveyed self-adjuvanting cancer nanovaccines in clinical research and discussed their advantages and challenges. In this review, we classified self-adjuvanting cancer nanovaccines according to the underlying immunomodulatory mechanism, which may provide mechanistic insights into the design of nanovaccines in the future.

Keywords: Antigen presentation; Cancer immunotherapy; Lymph node; Nanovaccine; Self-adjuvanting.

Fig. 1

Signaling pathways in vaccine adjuvant-activated APCs. APC antigen presenting cells; TLR Toll-like receptors; MyD88 myeloid differentiation factor 88; TIRAP Toll-interleukin receptor (TIR) domain containing adaptor protein; TRAM TIR-domain-containing adaptor-inducing interferon-β (TRIF); and TRIF-related adaptor molecule

Fig. 2

Enhancement of cross-presentation in dendritic cells by nanoparticles. A Schematic illustration of nanoparticles enhancing cross-presentation in dendritic cells. B Representative bright field (left), fluorescence (middle) and overlaid (right) images of DCs after incubation with FITC-labelled α-Al₂O₃ (60 nm)-OVA for 0.5 (upper) and 24 h (lower). C Vaccination with α-Al2O3-OVA induced high frequency of OVA-specific IFN-γ producing CD8⁺ T cells in spleens of mice [45]. Copyright 2011 Nature Publishing Group

Fig. 3

Potent tumor immunity induced by poly (γ-glutamic acid) nanovaccine via a TLR4 and MyD88 signaling pathway. A Schematic illustration of nasal vaccination with antigen-entrapping γ-PGA NPs evoked tumor immunity by eliciting antigen-specific CTLs. B Biodistribution of intranasally administered FITC-OVA/γ-PGA NPs. Green (FITC-OVA), red (rhodamine-labeled UEA-1), and blue (DAPI) signals were digitally merged. C Therapeutic effect of intranasal vaccination of OVA/γ-PGA NPs against B16-OVA lung metastasis. Reproduced with permission [54]. Copyright 2011 Elsevier B.V

Fig. 4

3DSNA nanovaccine activated the innate and specific immunity by the NF-κB signaling pathway. A Schematic of 3DSNA as versatile adjuvants that initiate antigen-specific CTL responses for cancer immunotherapy. B The analysis of p-p65 by laser scanning confocal microscopy. C The survival of tumor-bearing mice treated with different formulations after tumor challenge. Reproduced with permission [71]. Copyright 2019 Ivyspring International Publisher

Fig. 5

Adjuvants activated the NLRP3 inflammasome to improve the ability of nanovaccines to induce immune responses. A Model of mSP1000-induced IL-1β maturation via assembly of NALP3 inflammasomes. Reproduced with permission [81]. Copyright 2010 Elsevier Ltd. B Schematic illustration of Au4.5-induced NLRP3 inflammasome activation. Reproduced with permission [91]. Copyright 2020 American Chemical Society

Fig. 6

PC7A nanovaccine activated the STING pathway and inhibited tumor growth. A Schematic of the design and mechanism of the PC7A nanovaccine. B p-TBK1 is recruited into the STING–PC7A condensates. Reproduced with permission [98]. Copyright 2021 The Author(s), under exclusive licence to Springer Nature Limited. C Tumor growth inhibition study of B16F10 melanoma [97]. Copyright 2017 Nature Publishing Group

Fig. 7

self-adjuvanting effect of VLPs in cancer vaccines. A Key characteristics of VLPs. B T cell responses induced by VLP-based vaccines. C B cell responses induced by VLP-based vaccines. D Vaccines in the context of checkpoint inhibitors. Reproduced with permission [113]. Copyright 2020 The Author(s)