Anti-PD-L1 antibody retains antitumour effects while mitigating immunotherapy-related colitis in bladder cancer-bearing mice after CT-mediated intratumoral delivery

• Published in: International immunopharmacology 2024-08, Vol.137, p.112417, Article 112417
• Main Authors: Wang, Yin-Shuang, Zheng, Ai-Hong, Zhao, Jing-Wen, Gu, Hang-Yu, Meng, Zhuo-Nan, Chen, Jian-Yuan, Wang, Fu-Wei, Zhu, Xiu-Ming, Chen, Yuan, Xu, Song-Cheng, Sun, Li-Tao, Lai, Wing-Fu, Wu, Guo-Qing, Zhang, Da-Hong
• Format: Article
• Language: English
• Subjects: Animals; Anti-PD-L1 antibody; Antineoplastic Agents, Immunological - administration & dosage; Antineoplastic Agents, Immunological - therapeutic use; B7-H1 Antigen - antagonists & inhibitors; B7-H1 Antigen - immunology; Cell Line, Tumor; Colitis; Colitis - chemically induced; Colitis - drug therapy; Colitis - immunology; Colitis, Ulcerative - chemically induced; Colitis, Ulcerative - drug therapy; Colitis, Ulcerative - immunology; Controlled release; Curcumin - administration & dosage; Curcumin - therapeutic use; Disease Models, Animal; Drug Delivery Systems; Female; Humans; Immune Checkpoint Inhibitors - therapeutic use; Immunotherapy - methods; Local delivery; Mice; Mice, Inbred C57BL; Polymer; Tumor Microenvironment - drug effects; Tumor Microenvironment - immunology; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - immunology; Urinary Bladder Neoplasms - therapy
• ISSN: 1567-5769; 1878-1705; 1878-1705
• DOI: 10.1016/j.intimp.2024.112417

[Display omitted] •A biocompatible, gel-forming polymer was generated for drug delivery and controlled drug release.•The polymer-mediated local delivery of curcumin and anti-PD-L1 antibody elicited antitumor effect.•Intratumoral delivery of anti-PD-L1 antibody via the polymer was safe for mice with ulcerative colitis. 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.