Galstyan, Anna and Markman, Janet L. and Shatalova, Ekaterina S. and Chiechi, Antonella and Korman, Alan J. and Patil, Rameshwar and Klymyshyn, Dmytro and Tourtellotte, Warren G. and Israel, Liron L. and Braubach, Oliver and Ljubimov, Vladimir A. and Mashouf, Leila A. and Ramesh, Arshia and Grodzinski, Zachary B. and Penichet, Manuel L. and Black, Keith L. and Holler, Eggehard and Sun, Tao and Ding, Hui and Ljubimov, Alexander V. and Ljubimova, Julia Y. (2019) Blood-brain barrier permeable nano immunoconjugates induce local immune responses for glioma therapy. NATURE COMMUNICATIONS, 10: 3850. ISSN 2041-1723,
Full text not available from this repository. (Request a copy)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(ss-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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GLIOBLASTOMA ERADICATION; DELIVERY; BLOCKADE; PROTEIN; SYSTEM; IDENTIFICATION; IMMUNOTHERAPY; INTERLEUKIN-2; MACROPHAGES; ANAPHYLAXIS; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Alumni or Retired > Prof. Dr. Eggehard Holler |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 31 Mar 2020 09:15 |
| Last Modified: | 31 Mar 2020 09:15 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26399 |
Actions (login required)
 |
View Item |
