Dual Immunostimulatory Pathway Agonism through a Synthetic Nanocarrier Triggers Robust Anti-Tumor Immunity in Murine Glioblastoma

Dual Immunostimulatory Pathway Agonism through a Synthetic Nanocarrier Triggers Robust Anti-Tumor Immunity in Murine Glioblastoma

© 2022 The Authors. Advanced Materials published by Wiley-VCH GmbH.

Détails bibliographiques
Publié dans:Advanced materials (Deerfield Beach, Fla.). - 1998. - 35(2023), 7 vom: 12. Feb., Seite e2208782
Auteur principal: Lugani, Sophie (Auteur)
Autres auteurs: Halabi, Elias A, Oh, Juhyun, Kohler, Rainer H, Peterson, Hannah M, Breakefield, Xandra O, Chiocca, E Antonio A, Miller, Miles A, Garris, Christopher S, Weissleder, Ralph
Format: Article en ligne
Langue:English
Publié: 2023
Accès à la collection:Advanced materials (Deerfield Beach, Fla.)
Sujets:Journal Article IFNG glioblastoma interleukin-12 macrophage nanoparticles targeting Adjuvants, Immunologic
Description
Résumé:© 2022 The Authors. Advanced Materials published by Wiley-VCH GmbH.
Myeloid cells are abundant, create a highly immunosuppressive environment in glioblastoma (GBM), and thus contribute to poor immunotherapy responses. Based on the hypothesis that small molecules can be used to stimulate myeloid cells to elicit anti-tumor effector functions, a synthetic nanoparticle approach is developed to deliver dual NF-kB pathway-inducing agents into these cells via systemic administration. Synthetic, cyclodextrin-adjuvant nanoconstructs (CANDI) with high affinity for tumor-associated myeloid cells are dually loaded with a TLR7 and 8 (Toll-like receptor, 7 and 8) agonist (R848) and a cIAP (cellular inhibitor of apoptosis protein) inhibitor (LCL-161) to dually activate these myeloid cells. Here CANDI is shown to: i) readily enter the GBM tumor microenvironment (TME) and accumulate at high concentrations, ii) is taken up by tumor-associated myeloid cells, iii) potently synergize payloads compared to monotherapy, iv) activate myeloid cells, v) fosters a "hot" TME with high levels of T effector cells, and vi) controls the growth of murine GBM as mono- and combination therapies with anti-PD1. Multi-pathway targeted myeloid stimulation via the CANDI platform can efficiently drive anti-tumor immunity in GBM
Description:Date Completed 24.02.2023
Date Revised 30.09.2024
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-4095
DOI:10.1002/adma.202208782