| Autor: |
Anna Galstyan, Janet L. Markman, Ekaterina S. Shatalova, Antonella Chiechi, Alan J. Korman, Rameshwar Patil, Dmytro Klymyshyn, Warren G. Tourtellotte, Liron L. Israel, Oliver Braubach, Vladimir A. Ljubimov, Leila A. Mashouf, Arshia Ramesh, Zachary B. Grodzinski, Manuel L. Penichet, Keith L. Black, Eggehard Holler, Tao Sun, Hui Ding, Alexander V. Ljubimov, Julia Y. Ljubimova |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Nature Communications, Vol 10, Iss 1, Pp 1-13 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-019-11719-3 |
| Popis: |
Abstract Brain glioma treatment with checkpoint inhibitor antibodies to cytotoxic T-lymphocyte-associated antigen 4 (a-CTLA-4) and programmed cell death-1 (a-PD-1) was largely unsuccessful due to their inability to cross blood–brain barrier (BBB). Here we describe targeted nanoscale immunoconjugates (NICs) on natural biopolymer scaffold, poly(β-L-malic acid), with covalently attached a-CTLA-4 or a-PD-1 for systemic delivery across the BBB and activation of local brain anti-tumor immune response. NIC treatment of mice bearing intracranial GL261 glioblastoma (GBM) results in an increase of CD8+ T cells, NK cells and macrophages with a decrease of regulatory T cells (Tregs) in the brain tumor area. Survival of GBM-bearing mice treated with NIC combination is significantly longer compared to animals treated with single checkpoint inhibitor-bearing NICs or free a-CTLA-4 and a-PD-1. Our study demonstrates trans-BBB delivery of tumor-targeted polymer-conjugated checkpoint inhibitors as an effective GBM treatment via activation of both systemic and local privileged brain tumor immune response. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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