2023 World Conference on Lung Cancer (Posters)-P2.21. A Combination of PD-1 and TIGIT Checkpoint Blockade Elicits a Strong Antitumor Response in the Patient and Mouse Pleural Mesothelioma Model

P2.21. A Combination of PD-1 and TIGIT Checkpoint Blockade Elicits a Strong Antitumor Response in the Patient and Mouse Pleural Mesothelioma Model - PDF(Abstract)

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This study investigates a combination of PD-1 and TIGIT checkpoint blockade as a potential treatment for pleural mesothelioma (PM) in a mouse model. PM is a aggressive cancer of the lung lining with limited treatment options. Immunotherapy has shown promise in PM, with single-agent anti-PD-1 antibodies reporting tumour response rates of 10-20% and combination immunotherapy with ipilimumab and nivolumab increasing the response rate to about 40%. However, the use of CTLA-4 inhibitors are associated with severe immune-related adverse events. In this study, the researchers explored the combination of PD-1 and TIGIT blockade in a mouse PM model.<br /><br />Ninety mice were injected with PM cells and divided into nine groups to receive different treatments. The researchers assessed tumour response, functional state of T cells, and survival rate. The results showed that the combination of anti-PD-1/TIGIT antibodies demonstrated a better anti-tumour response compared to anti-PD-1/CTLA-4 or single-agent treatments. Mice treated with anti-PD-1/TIGIT antibodies achieved complete tumour regression with increased regulatory T cells, CD8 T cells, CD4 T cells, and NK cells. These mice remained tumour-free for more than 300 days without any adverse events. Additionally, they were resistant to tumor rechallenge after the elimination of initial tumors.<br /><br />The researchers concluded that the combination of anti-PD-1 and anti-TIGIT antibodies induced a 90% response rate in the mouse PM model with long-term immunological memory function. This combination was more effective and had no observed adverse effects compared to the standard combination of anti-PD-1/CTLA-4. These findings suggest a biological rationale for a clinical trial using the anti-PD-1/TIGIT combination immunotherapy in PM patients.

Asset Subtitle

Huaikai Shi

Meta Tag

Speaker Huaikai Shi

Topic Mesothelioma, Thymoma & Other Thoracic Tumors: Translational

Keywords

PD-1

TIGIT

checkpoint blockade

pleural mesothelioma

mouse model

immunotherapy

anti-PD-1 antibodies

ipilimumab

nivolumab

CTLA-4 inhibitors