Subcutaneous Nanodisc Vaccination with Neoantigens for Combination Cancer Immunotherapy

Bioconjugate Chemistry
Rui KuaiJames J Moon

Abstract

While cancer immunotherapy provides new exciting treatment options for patients, there is an urgent need for new strategies that can synergize with immune checkpoint blockers and boost the patient response rates. We have developed a personalized vaccine nanodisc platform based on synthetic high-density lipoproteins for co-delivery of immunostimulatory agents and tumor antigens, including tumor-specific neoantigens. Here we examined the route of delivery, safety profiles, and therapeutic efficacy of nanodisc vaccination against established tumors. We report that nanodiscs administered via the subcutaneous (SC) or intramuscular (IM) routes were well tolerated in mice without any signs of toxicity. The SC route significantly enhanced nanoparticle delivery to draining lymph nodes, improved nanodisc uptake by antigen-presenting cells, and generated 7-fold higher frequency of neoantigen-specific T cells, compared with the IM route. Importantly, when mice bearing advanced B16F10 melanoma tumors were treated with nanodiscs plus anti-PD-1 and anti-CTLA-4 IgG therapy, the combination immunotherapy exerted potent antitumor efficacy, leading to eradication of established tumors in ∼60% of animals. These results demonstrate nanodiscs custom...Continue Reading

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Citations

Oct 1, 2019·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Yuhao HaoYuanzeng Min
May 14, 2020·Expert Opinion on Investigational Drugs·Maria B Garcia-FabianiMaria G Castro
Jun 8, 2019·Annual Review of Chemical and Biomolecular Engineering·Alexandra N Tsoras, Julie A Champion
Mar 3, 2020·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Jingxing Yang, Chunfu Zhang
Jun 30, 2019·Advanced Materials·C Wyatt ShieldsSamir Mitragotri
Aug 14, 2019·Nature Biomedical Engineering·Lindsay ScheetzJames J Moon
Mar 11, 2020·International Journal of Molecular Sciences·Lindsay M ScheetzAnna Schwendeman
May 2, 2019·Frontiers in Immunology·Felix L FennemannMartijn Verdoes
Oct 8, 2020·Cell Transplantation·M Rezaa MohammadiJonathan Rt Lakey
May 23, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Lindsay ScheetzJames J Moon
Mar 13, 2021·Advanced Drug Delivery Reviews·Carina PeresHelena F Florindo
Apr 30, 2020·Cell Reports·Kimmo RantalainenAndrew B Ward
Jul 3, 2021·Polymers·Teresa BasinskaStanislaw Slomkowski
Apr 9, 2020·Acta Biomaterialia·Prateek BhardwajRinti Banerjee
Oct 6, 2020·Accounts of Chemical Research·Marisa E AikinsJames J Moon
May 30, 2019·Langmuir : the ACS Journal of Surfaces and Colloids·Yan GeZhenhui Qi
Sep 12, 2020·Chemical Reviews·Wen-Hao Li, Yan-Mei Li
Aug 18, 2021·Advanced Drug Delivery Reviews·Tong YeWei Wei
Sep 15, 2020·Nano Letters·Alireza Hassani NajafabadiJames J Moon
Jul 24, 2020·Bioconjugate Chemistry·Martine DarwishCraig Blanchette

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