sabatolimab是一种针对TIM-3受体具有免疫髓系活性的新型免疫疗法。

IF 4.1 Q2 IMMUNOLOGY Immunotherapy advances Pub Date : 2022-01-01 DOI:10.1093/immadv/ltac019

Stephanie Schwartz, Nidhi Patel, Tyler Longmire, Pushpa Jayaraman, Xiaomo Jiang, Hongbo Lu, Lisa Baker, Janelle Velez, Radha Ramesh, Anne-Sophie Wavreille, Melanie Verneret, Hong Fan, Tiancen Hu, Fangmin Xu, John Taraszka, Marc Pelletier, Joy Miyashiro, Mikael Rinne, Glenn Dranoff, Catherine Sabatos-Peyton, Viviana Cremasco

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引用次数: 16

摘要

目的:Sabatolimab是一种人源化单克隆抗体(hIgG4, S228P)，靶向人t细胞免疫球蛋白结构域和粘蛋白结构域3 (TIM-3)。在这里，我们描述了sabatolimab的发展和特性。方法:测定Sabatolimab与靶点TIM-3的结合及阻断作用。在t细胞杀伤和骨髓细胞因子试验中检测了sabatolimab的功能效应。同时对抗体介导的细胞吞噬作用(ADCP)进行了评估。结果:Sabatolimab显示:(i)增强树突状细胞(dc)对t细胞的杀伤和炎症细胞因子的产生;(ii)促进表达tim -3的靶细胞的吞噬摄取;(iii)阻断TIM-3与其配体PtdSer/galectin-9之间的相互作用。结论:综上所述，我们的研究结果支持sabatolimab的直接抗白血病作用和免疫介导的调节作用，强化了sabatolimab代表一种具有免疫髓细胞活性的新型免疫疗法的概念，有望治疗髓细胞肿瘤。

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Characterization of sabatolimab, a novel immunotherapy with immuno-myeloid activity directed against TIM-3 receptor.

Objectives: Sabatolimab is a humanized monoclonal antibody (hIgG4, S228P) directed against human T-cell immunoglobulin domain and mucin domain-3 (TIM-3). Herein, we describe the development and characterization of sabatolimab.

Methods: Sabatolimab was tested for binding to its target TIM-3 and blocking properties. The functional effects of sabatolimab were tested in T-cell killing and myeloid cell cytokine assays. Antibody-mediated cell phagocytosis (ADCP) by sabatolimab was also assessed.

Results: Sabatolimab was shown to (i) enhance T-cell killing and inflammatory cytokine production by dendritic cells (DCs); (ii) facilitate the phagocytic uptake of TIM-3-expressing target cells; and (iii) block the interaction between TIM-3 and its ligands PtdSer/galectin-9.

Conclusion: Taken together, our results support both direct anti-leukemic effects and immune-mediated modulation by sabatolimab, reinforcing the notion that sabatolimab represents a novel immunotherapy with immuno-myeloid activity, holding promise for the treatment of myeloid cell neoplasms.

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