Wang, Y.-S., Zheng, A.-H., Zhao, J.-W. et al. (11 more authors) (2024) Anti-PD-L1 antibody retains antitumour effects while mitigating immunotherapy-related colitis in bladder cancer-bearing mice after CT-mediated intratumoral delivery. International Immunopharmacology, 137. 112417. ISSN 1567-5769
Abstract
Drug local delivery system that directly supply anti-cancer drugs to the tumor microenvironment (TME) results in excellent tumor control and minimizes side effects associated with the anti-cancer drugs. Immune checkpoint inhibitors (ICIs) have been the mainstay of cancer immunotherapy. However, the systemic administration of ICIs is accompanied by considerable immunotherapy-related toxicity. To explore whether an anti-PD-L1 antibody administered locally via a sustained-release gel-forming carrier retains its effective anticancer function while causing fewer colitis-like side effects, CT, a previously reported depot system, was used to locally deliver an anti-PD-L1 antibody together with curcumin to the TME in bladder cancer-bearing ulcerative colitis model mice. We showed that CT-mediated intratumoral coinjection of an anti-PD-L1 antibody and curcumin enabled sustained release of both the loaded anti-PD-L1 antibody and curcumin, which contributed to substantial anticancer effects with negligible side effects on the colons of the UC model mice. However, although the anti-PD-L1 antibody administered systemically synergized with the CT-mediated intratumoral delivery of curcumin in inhibiting tumour growth, colitis was significantly worsened by intraperitoneal administration of anti-PD-L1 antibody. These findings suggested that CT is a promising agent for the local delivery of anticancer drugs, as it can allow effective anticancer functions to be retained while sharply reducing the adverse side effects associated with the systemic administration of these drugs.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2024, Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/. This is an author produced version of an article published in International Immunopharmacology. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Polymer; Local delivery; Controlled release; Anti-PD-L1 antibody; Colitis |
Dates: |
|
Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Environment (Leeds) > School of Food Science and Nutrition (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 11 Sep 2024 12:57 |
Last Modified: | 11 Sep 2024 12:57 |
Published Version: | https://www.sciencedirect.com/science/article/pii/... |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.intimp.2024.112417 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:217082 |
Download
