Sabatolimab TIM-3-targeting monoclonal antibody Treatment of myelodysplastic syndrome Treatment of acute myeloid leukemia

Immunotherapy has revolutionized the treatment of malignancies over the last 20 years, and new discoveries show potential for improvement in this area. T-cell immunoglobulin mucin receptor 3 (TIM-3) is an inhibitory receptor expressed on immune cells that regulates both innate and adaptive immune responses. In addition, TIM-3 maintains the self-renewal ability of leukemic stem cells through the activation of the 13-catenin and mTOR pathways. TIM-3 blockade is being studied as a new way to augment the anticancer response. Sabatolimab (MBG-453) is a high-affinity, humanized antibody targeting TIM-3. Based on the results of a dose-finding study, the recommended phase II dose was established at 800 mg every 4 weeks, with alternative dosing schedules of 600 mg every 3 or 400 mg every 2 weeks. Ongoing clinical trials with sabatolimab are concentrating on patients with myeloid malignancies, such as acute myeloid leukemia, myelodysplastic syndromes and chronic myelomonocytic leukemia, usually combining sabatolimab with low-intensity therapy (hypomethylating agents and/or venetoclax). Two studies involve patients with advanced or metastatic solid tumors and glioblastoma multiforme. The standalone efficacy of sabatolimab in the therapy of solid cancers is not established, but the co-blockade of PD-1 and TIM-3 can be adopted in the clinical field. Studies in myeloid malignancies show promising perspectives, especially on adopting this as the standard of care in heavily pretreated patients.