Shi, Huaikai and Yu, Ta-Kun and Johnson, Ben and Selvamani, Sakthi Priya and Zhuang, Ling and Lee, Kenneth and Klebe, Sonja and Smith, Samuel and Wong, Kirby and Chen, Kate and Clark, Georgina and Rath, Emma M. and Pearson, Holly and Ortega, David Gallego and Linton, Anthony and Kao, Steven and Silveira, Pablo and Cheng, Yuen Yee (2025) A combination of PD-1 and TIGIT immune checkpoint inhibitors elicits a strong anti-tumour response in mesothelioma. Journal of Experimental & Clinical Cancer Research, 44 (1). ISSN 1756-9966
Full text not available from this repository.Abstract
Abstract Background
Finding effective and curative treatment for mesothelioma remains challenging. While the introduction of immunotherapy combinations using ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) have offered hope for some patients, a large proportion of mesothelioma cases, particularly the epithelial subtype, have minimal benefit from this.
Methods
Our study was inspired by the results of the AdvanTG-105 phase I clinical trial, which showed partial response with anti-TIGIT/PD-1 treatment in two epithelioid mesothelioma patients. Here, we conducted a comprehensive in vivo experiment involving eight animal treatment groups administered with either PBS (control group), cisplatin/pemetrexed, anti-PD-1, anti-PD-1 + anti-CTLA-4, anti-TIGIT, anti-PD-1 + anti-TIGIT, anti-PD-1 + anti-CTLA-4 + anti-TIGIT, and cisplatin/pemetrexed + anti-PD-1 + anti-TIGIT.
Results
Our results indicate that animals receiving anti-PD-1 + TIGIT exhibited a superior anti-tumour response, with 90% of the treatment group exhibiting an objective response, compared to 60%, 20% and 40% for the standard-of-care anti-PD-1 + CTLA-4, single-agent anti-PD-1 and cisplatin/pemetrexed treatment groups, respectively. Animals receiving anti-PD-1 + TIGIT displayed a significantly reduced average tumour size, with improved weight and survival rates, and fewer adverse effects than those receiving anti-PD-1 + CTLA-4 treatment. Anti-PD-1 + TIGIT-treated animals achieved complete tumour regression, with heightened effector CD8 + T cell and NK cell activity, remaining tumour-free for over 300 days without immune-related adverse events. After initial tumour elimination, anti-PD-1 + TIGIT-treated animals showed no tumour regrowth in the rechallenge experiment.
Conclusion
These findings provide rationale for the development of an anti-PD-1 + TIGIT combination immunotherapy trial for mesothelioma patients.
Graphical Abstract
Top) The comparison of standard-of-care treatment and anti-TIGIT novel combination treatment in the mesothelioma animal models, with an example of response treated with tislelizumab and ociperlimab in a pleural mesothelioma patient in the AdvanTIG-105 study. The number of animals/patients treated and the number of treatment responders are presented. Bottom) Schematic illustration of anti-tumour immune response at the cellular level induced by anti-PD-1/TIGIT checkpoint blockade for efficient cancer immunotherapy.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 05 May 2025 06:01 |
| Last Modified: | 05 May 2025 06:01 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/1674 |
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