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ITK Inhibitor Soquelitinib Combined with CAR-T Therapy Significantly Enhances Antitumor Efficacy
Angel Pharmaceuticals, together with Peking University Cancer Hospital and other institutions, has conducted in-depth research on the combination of an ITK inhibitor with CAR-T therapy, demonstrating for the first time that the ITK inhibitor soquelitinib can significantly enhance the efficacy of anti-CD19 CAR-T cells and exploring the underlying molecular mechanisms. The research findings were published in Cell Death Discovery, a journal under Nature Publishing Group.
The team employed dual strategies of gene knockout and pharmacological inhibition, combined with flow cytometry, RNA sequencing, and lymphoma mouse models, to systematically evaluate the impact of ITK inhibition on CAR-T cell function. Co-administration with soquelitinib significantly enhanced the viability, cytotoxicity, and antitumor activity of CAR-T cells. Soquelitinib prevented T-cell exhaustion by inhibiting key pathways involved in T-cell exhaustion, increased the expression of CAR-T cytotoxic molecules (GZMB/TNF-α/IFN-γ) by 2–3 fold, and expanded CD8+ effector T cells by 1.5-fold, thereby extending the survival of B-cell lymphoma-bearing mice by 18%. This breakthrough discovery provides a new therapeutic approach for patients with B-cell lymphomas and solid tumors.
For more details on the study, please refer to the following link: https://doi.org/10.1038/s41420-026-03004-2
About Soquelitinib
Soquelitinib (CPI-818) is the world's first clinical-stage, highly selective, oral small-molecule ITK inhibitor. ITK (interleukin-2-inducible T-cell kinase) is primarily expressed in T cells and plays a role in the immune function of T cells and natural killer (NK) cells. Studies have shown that soquelitinib can influence T-cell differentiation, induce the production of Th1 helper cells, while blocking the development of Th2 and Th17 cells and their cytokine production. Th1 cell immunity is the primary immune pathway for antitumor responses, viral infections, and other endogenous antigens. Th2 and Th17 cells are more commonly associated with tumors, autoimmune diseases, and allergic conditions. The company believes that inhibiting this specific molecular target in T cells may have therapeutic benefits for patients with cancers, including solid tumors, as well as those with autoimmune and allergic diseases. Recent studies have shown that ITK controls the switch between Th17 cells (pro-inflammatory) and regulatory T cells (Tregs, anti-inflammatory). Inhibiting ITK promotes T-cell differentiation toward Treg cells, potentially suppressing autoimmune and inflammatory responses. Angel Pharmaceuticals holds the rights to soquelitinib in Greater China.
About Angel Pharmaceuticals
Angel Pharmaceuticals is a biopharmaceutical company focused on innovative therapies for immune modulation, committed to developing breakthrough drugs to improve the treatment of cancer, autoimmune diseases, and inflammatory disorders by targeting key signaling pathways in T and B cells. The company is co-invested by Beta Fund, Hisun Pharmaceuticals, Tigermed, and Puhua Investment, and has established a strategic partnership with Corvus Pharmaceuticals (CRVS) of the U.S. For more information, please visit www.angelpharma.com.
