Robust Anti‐Tumor T Cell Response with Efficient Intratumoral Infiltration by Nanodisc Cancer Immunotherapy

Abstract

Potent anti‐tumor T cell response and efficient intratumoral T cell infiltration are the major challenges for therapeutic cancer vaccines. To address these issues, a nanovaccine system is designed to promote anti‐tumor T cell responses, and intratumoral infiltration is examined in various murine tumor models. Subcutaneous vaccination with nanodiscs carrying human papillomavirus (HPV)‐16 E7 antigen elicits as high as ∼32% E7‐specific CD8α+ T cell responses in circulation, representing a 29‐fold improvement over the soluble peptide vaccination. Importantly, nanodisc vaccination also promotes robust intratumoral T cell infiltration and eliminates HPV16 E6/E7‐expressing TC‐1 tumors at mucosal sites, including lungs, inner lip, and intravaginal tissues. In a benchmark study with a live Listeria vaccine combined with anti‐PD‐1 IgG, nanodiscs plus anti‐PD‐1 immune checkpoint blockade elicits comparable levels of T cell responses with anti‐tumor efficacy. Furthermore, compared with Complete Freund's Adjuvant combined with tetanus toxoid, nanodisc vaccination in HLA‐A02 mice generates >200‐fold stronger IFN‐γ+ T cell responses against a neoantigen from an HLA‐A02 melanoma patient. Overall, these results show that the nanodisc system is a promising cancer vaccine platform for inducing anti‐tumor T cell responses.

Nanodiscs: a versatile nanocarrier platform for cancer diagnosis and treatment

“…LNDs consist of a disc-shaped lipid bilayer (typical diameter B10-20 nm) surrounded and stabilized by amphiphilic biomacromolecules such as Apolipoprotein A1 (apoA-1) or membrane scaffold proteins (MSPs; Fig. 2A), 28,29 saposin, 30 peptides, 31 or nucleic acids; 32 (2) Styrene-maleic acid (SMA) lipid nanoparticles (SMALPs), which differ from LNDs in that the amphiphilic membrane scaffold biomacromolecules in LNDs are replaced with synthetic SMA or SMA-like copolymers (Fig. 2B); [33][34][35][36][37] (3) Polymer nanodiscs (PNDs).…”

Nano-bio interfaces effect of two-dimensional nanomaterials and their applications in cancer immunotherapy

“…Kuai et al. 70 developed several nanodiscs vaccines. For example, they fabricated high-density lipoprotein (HDL) nanodiscs for antigen and immunostimulatory agent delivery ( Fig.…”

“…Reprinted with permission from Ref. 70 . Copyright © 2020 Wiley-VCH GmbH, Weinheim; (B) Subcutaneous administration of nanodiscs and neoantigens for immunotherapy.…”

“…Overall, these sandwich type biosensors not only exhibit high capability of antigen loading, but also hold advantages in protecting antibodies from physiological environment. Overall, these sandwich type biosensors not only exhibit high capability of antigen loading, but also hold advantages in protecting antibodies from physiological environment ( Table 1 58 , 59 , 60 , 61 , 64 , 65 , 66 , 69 , 70 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 84 , 85 , 86 , 87 , 88 , 89 , 90 ).

Figure 10 (A) Detection mechanism of the Mxene-based biosensor.

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“… 2D nanomaterial Advantage Disadvantage Application Ref. GO High loading efficacy, high aspect ratio and surface area Hard preparation, poor water solubility Antigen delivery, immune biosensing 58 , 59 , 89 LDH Good biocompatibility, high payload loading capacity, controllable size, easy and low-cost preparation Antigen delivery 60 Chitosan/calcium phosphate Easy and low-cost preparation, biocompatible, bioresorbable Low efficacy of immune response Antigen delivery 61 HDL nanodiscs Safety, long term circulation, prolonged antigen presentation and immune response Adjuvants and immune modulators delivery 64 , 65 , 66 , 70 BP High photothermal convention efficacy, rapid internalization, biodegradability, biocompatibility, in situ activation of necroptosis Sensitive to oxygen and water, high bandgap Immune modulators delivery, PTT, photoimmunotherapy, PDT 69 , 74 , 75 , 76 Pd nanosheets High photothermal convention efficiency, controllable size, strong plasmon absorption in NIR Photoimmunotherapy 77 MoS 2 High photothermal convention efficiency, dye quenchers ability, strong NIR photothermal absorption, biocompatibility, water solubility Difficulty in treatment of metastatic tumor Photoimmunotherapy, immune biosensing 78 , 79 , 88 MOF High ROS generation, high capability of antigen loading, structural tunability, synthetic flexibility, biocompatibility, high porosity Poor stability Radiotherapy, immunotherapy, radiodynamic therapy, CDT, PDT, immune biosensing ...…”