Deliver anti-PD-L1 into brain by p-hydroxybenzoic acid to enhance immunotherapeutic effect for glioblastoma
| Autor: | Cao Xie, Yu Liu, Linwei Lu, Dongli Wang, Jinyang Li, Haiyan Guo, Ruifeng Wang, Jianfen Zhou, Zhilan Chai, Weiyue Lu, Songli Wang, Shengyu Yao |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Programmed Cell Death 1 Receptor
Pharmaceutical Science 02 engineering and technology B7-H1 Antigen 03 medical and health sciences Glioma Hydroxybenzoates medicine Humans Distribution (pharmacology) 030304 developmental biology 0303 health sciences biology Brain Neoplasms Chemistry Brain 021001 nanoscience & nanotechnology medicine.disease Blockade Transcytosis Dopamine receptor biology.protein Cancer research Immunotherapy Antibody Glioblastoma 0210 nano-technology Conjugate |
| Zdroj: | Journal of Controlled Release. 320:63-72 |
| ISSN: | 0168-3659 |
| DOI: | 10.1016/j.jconrel.2020.01.005 |
| Popis: | In glioblastoma with typical immunosuppressive characteristics, immune checkpoint inhibitors treatment showed unsatisfactory clinical effects, attributable to the exclusion of antibodies by blood-brain barrier (BBB) to a large extent. Herein, a conjugate of anti-programmed death ligand 1 antibody (αPDL1) and the targeting moiety p-hydroxybenzoic acid (pHA) was designed to realize crossing BBB of antibody based on the dopamine receptor mediated transcytosis. Conjugation with pHA did not influence the binding affinity of αPDL1 with PD-L1 protein, thus maintaining the capability of PD pathway blockade. Importantly, pHA-αPDL1 crossed BBB, demonstrated by the increased distribution in both the brain and the glioma after intravenous administration of pHA-αPDL1. Compared with the unmodified αPDL1, pHA-αPDL1 prolonged the survival time and suppressed tumor growth more effectively in an orthotopic glioblastoma model by activating glioma-infiltrating T cells. Our results suggested the potential of the antibody-pHA conjugate to improve efficacy for cerebral diseases by providing a potential platform for macromolecules to play therapeutics role in the brain. |
| Databáze: | OpenAIRE |
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