Sabatolimab
(Synonyms: MBG453) 目录号 : GC64424
Sabatolimab (anti-TIM-3) (MBG453, NVP-MBG453) is a high-affinity, humanized IgG4 antibody targeting TIM-3 on the surface of T-cells.
Cas No.:2252262-24-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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Purity: >98.00%
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Sabatolimab (anti-TIM-3) (MBG453, NVP-MBG453) is a high-affinity, humanized IgG4 antibody targeting TIM-3 on the surface of T-cells.
[1] Andrew M. Brunner, MD, et al. Blood (2020) 136 (Supplement 1): 1–2.
| Cas No. | 2252262-24-9 | SDF | Download SDF |
| 别名 | MBG453 | ||
| 分子式 | 分子量 | ||
| 溶解度 | 储存条件 | Store at -20°C | |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Phase I/Ib Clinical Trial of Sabatolimab, an Anti-TIM-3 Antibody, Alone and in Combination with Spartalizumab, an Anti-PD-1 Antibody, in Advanced Solid Tumors
Clin Cancer Res 2021 Jul 1;27(13):3620-3629.PMID:33883177DOI:10.1158/1078-0432.CCR-20-4746.
Purpose: Sabatolimab (MBG453) and spartalizumab are mAbs that bind T-cell immunoglobulin domain and mucin domain-3 (TIM-3) and programmed death-1 (PD-1), respectively. This phase I/II study evaluated the safety and efficacy of Sabatolimab, with or without spartalizumab, in patients with advanced solid tumors. Patients and methods: Primary objectives of the phase I/Ib part were to characterize the safety and estimate recommended phase II dose (RP2D) for future studies. Dose escalation was guided by a Bayesian (hierarchical) logistic regression model. Sabatolimab was administered intravenously, 20 to 1,200 mg, every 2 or 4 weeks (Q2W or Q4W). Spartalizumab was administered intravenously, 80 to 400 mg, Q2W or Q4W. Results: Enrolled patients (n = 219) had a range of cancers, most commonly ovarian (17%) and colorectal cancer (7%); patients received Sabatolimab (n = 133) or Sabatolimab plus spartalizumab (n = 86). The MTD was not reached. The most common adverse event suspected to be treatment-related was fatigue (9%, Sabatolimab; 15%, combination). No responses were seen with Sabatolimab. Five patients receiving combination treatment had partial responses (6%; lasting 12-27 months) in colorectal cancer (n = 2), non-small cell lung cancer (NSCLC), malignant perianal melanoma, and SCLC. Of the five, two patients had elevated expression of immune markers in baseline biopsies; another three had >10% TIM-3-positive staining, including one patient with NSCLC who received prior PD-1 therapy. Conclusions: Sabatolimab plus spartalizumab was well tolerated and showed preliminary signs of antitumor activity. The RP2D for Sabatolimab was selected as 800 mg Q4W (alternatively Q3W or Q2W schedules, based on modeling), with or without 400 mg spartalizumab Q4W.
Advances in myelodysplastic syndrome
Curr Opin Oncol 2021 Nov 1;33(6):681-686.PMID:34474438DOI:10.1097/CCO.0000000000000790.
Purpose of review: In this review, the focus is on the most recent improvements in diagnosis, prognostication and therapy of myelodysplastic syndromes (MDS) and on their relevance for clinical management. Recent findings: Analytical methods to refine cytogenetic and molecular assessment of MDS have been proposed, improving prognostic stratification obtained from integration of clinical and genomic data. Novel agents with very different mode of action, as single drugs or added to HMA backbone, show promising clinical results in LR-MDS and HR-MDS. Luspatercept has obtained approval given the fact that in transfusion-dependent erythropoietic-stimulating agent resistant/relapsed LR-MDS induced nearly 50% of transfusion independence. Another investigational agent showing efficacy and possibly disease modifying activity in the same setting is the telomerase inhibitor imetelstat. Results from phase II study with azacytidine and pevonedistat indicate the concrete possibility to enhance durable responses compared with azacitidine single drug. In the same direction are the preliminary results of other agents with different mode of action: magrolimab, venetoclax, Sabatolimab, as well as the targeted therapy with enasidenib and ivosidenib. New posttransplant maintenance strategies may concur to prolong response. Summary: Better diagnosis and prognostic stratification may allow a more precise and personalized treatment of MDS with novel agent combinations leading to improved therapeutic algorithms.
Characterization of Sabatolimab, a novel immunotherapy with immuno-myeloid activity directed against TIM-3 receptor
Immunother Adv 2022 Aug 10;2(1):ltac019.PMID:36196369DOI:10.1093/immadv/ltac019.
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.
Immune Checkpoint Inhibition in Acute Myeloid Leukemia and Myelodysplastic Syndromes
Cells 2022 Jul 20;11(14):2249.PMID:35883692DOI:10.3390/cells11142249.
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of many solid tumors, with limited progress made in the area of myeloid malignancies. The low mutational burden of acute myeloid leukemia (AML) is one potential reason behind the lack of activity of T-cell harnessing ICIs, particularly CTLA-4 and PD-1 inhibitors. Innate immune checkpoints play a critical role in the immune escape of AML and myelodysplastic syndromes (MDS). The CD47 targeting agent, magrolimab, has shown promising activity when combined with azacitidine in early phase trials conducted in AML and higher-risk MDS, especially among patients harboring a TP53 mutation. Similarly, Sabatolimab (an anti-TIM-3 monoclonal antibody) plus hypomethylating agents have shown durable responses in higher-risk MDS and AML in early clinical trials. Randomized trials are currently ongoing to confirm the efficacy of these agents. In this review, we will present the current progress and future directions of immune checkpoint inhibition in AML and MDS.
New Frontiers in Monoclonal Antibodies for the Targeted Therapy of Acute Myeloid Leukemia and Myelodysplastic Syndromes
Int J Mol Sci 2022 Jul 7;23(14):7542.PMID:35886899DOI:10.3390/ijms23147542.
Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) represent an unmet clinical need whose prognosis is still dismal. Alterations of immune response play a prominent role in AML/MDS pathogenesis, revealing novel options for immunotherapy. Among immune system regulators, CD47, immune checkpoints, and toll-like receptor 2 (TLR2) are major targets. Magrolimab antagonizes CD47, which is overexpressed by AML and MDS cells, thus inducing macrophage phagocytosis with clinical activity in AML/MDS. Sabatolimab, an inhibitor of T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3), which disrupts its binding to galectin-9, has shown promising results in AML/MDS, enhancing the effector functions of lymphocytes and triggering tumor cell death. Several other surface molecules, namely CD33, CD123, CD45, and CD70, can be targeted with monoclonal antibodies (mAbs) that exert different mechanisms of action and include naked and conjugated antibodies, bispecific T-cell engagers, trispecific killer engagers, and fusion proteins linked to toxins. These novel mAbs are currently under investigation for use as monotherapy or in combination with hypomethylating agents, BCL2 inhibitors, and chemotherapy in various clinical trials at different phases of development. Here, we review the main molecular targets and modes of action of novel mAb-based immunotherapies, which can represent the future of AML and higher risk MDS treatment.