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Anti-PD-L1 antibody retains antitumour effects while mitigating immunotherapy-related colitis in bladder cancer-bearing mice after CT-mediated intratumoral delivery.
- Source :
-
International immunopharmacology [Int Immunopharmacol] 2024 Aug 20; Vol. 137, pp. 112417. Date of Electronic Publication: 2024 Jun 18. - Publication Year :
- 2024
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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.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Mice
Humans
Cell Line, Tumor
Female
Colitis chemically induced
Colitis immunology
Colitis drug therapy
Tumor Microenvironment drug effects
Tumor Microenvironment immunology
Drug Delivery Systems
Disease Models, Animal
Mice, Inbred C57BL
Antineoplastic Agents, Immunological administration & dosage
Antineoplastic Agents, Immunological therapeutic use
Colitis, Ulcerative chemically induced
Colitis, Ulcerative drug therapy
Colitis, Ulcerative immunology
Urinary Bladder Neoplasms drug therapy
Urinary Bladder Neoplasms immunology
Urinary Bladder Neoplasms therapy
B7-H1 Antigen antagonists & inhibitors
B7-H1 Antigen immunology
Curcumin therapeutic use
Curcumin administration & dosage
Immunotherapy methods
Immune Checkpoint Inhibitors therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1705
- Volume :
- 137
- Database :
- MEDLINE
- Journal :
- International immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 38897122
- Full Text :
- https://doi.org/10.1016/j.intimp.2024.112417