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首页> 外文期刊>Clinical cancer research: an official journal of the American Association for Cancer Research >SAR3419: an anti-CD19-Maytansinoid Immunoconjugate for the treatment of B-cell malignancies.
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SAR3419: an anti-CD19-Maytansinoid Immunoconjugate for the treatment of B-cell malignancies.

机译：SAR3419：抗CD19-美登木素生物碱免疫共轭物，用于治疗B细胞恶性肿瘤。

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摘要

SAR3419 is a novel anti-CD19 humanized monoclonal antibody conjugated to a maytansine derivate through a cleavable linker for the treatment of B-cell malignancies. SAR3419 combines the strengths of a high-potency tubulin inhibitor and the exquisite B-cell selectivity of an anti-CD19 antibody. The internalization and processing of SAR3419, following its binding at the surface of CD19-positive human lymphoma cell lines and xenograft models, release active metabolites that trigger cell-cycle arrest and apoptosis, leading to cell death and tumor regression. SAR3419 has also been shown to be active in different lymphoma xenograft models, including aggressive diffuse large B-cell lymphoma, resulting in complete regressions and tumor-free survival. In these models, the activity of SAR3419 compared favorably with rituximab and lymphoma standard of care chemotherapy. Two phase I trials with 2 different schedules of SAR3419 as a single agent were conducted in refractory/relapsed B-cell non-Hodgkin lymphoma. Activity was reported in both schedules, in heavily pretreated patients of both follicular and diffuse large B-cell lymphoma subtypes, with a notable lack of significant hematological toxicity, validating SAR3419 as an effective antibody-drug conjugate and opening opportunities in the future. Numerous B-cell-specific anti-CD19 biologics are available to treat B-cell non-Hodgkin lymphoma, and early phase I results obtained with SAR3419 suggest that it is a promising candidate for further development in this disease. In addition, thanks to the broad expression of CD19, SAR3419 may provide treatment options for B-cell leukemias that are often CD20-negative.
机译：SAR3419是一种新型抗CD19人源化单克隆抗体，通过可裂解的接头与美登素衍生物偶联，用于治疗B细胞恶性肿瘤。 SAR3419结合了高效微管蛋白抑制剂的优势和抗CD19抗体的出色B细胞选择性。 SAR3419在CD19阳性人类淋巴瘤细胞系和异种移植模型表面结合后，其内在化和加工过程释放出活性代谢产物，触发细胞周期停滞和凋亡，导致细胞死亡和肿瘤消退。 SAR3419在不同的淋巴瘤异种移植模型（包括侵袭性弥漫性大B细胞淋巴瘤）中也表现出活性，导致完全消退和无肿瘤生存。在这些模型中，SAR3419的活性优于利妥昔单抗和淋巴瘤护理化疗标准。在难治性/复发性B细胞非霍奇金淋巴瘤中进行了两项I期试验，以两种不同的SAR3419方案作为单一药物。在两个时间表中均报告了活性，在经过预处理的滤泡性和弥漫性大B细胞淋巴瘤亚型患者中，明显缺乏显着的血液学毒性，从而证实SAR3419作为有效的抗体-药物偶联物并在将来有发展的机会。许多B细胞特异性抗CD19生物制剂可用于治疗B细胞非霍奇金淋巴瘤，SAR3419获得的I期早期结果表明，它是该疾病进一步发展的有希望的候选者。此外，由于CD19的广泛表达，SAR3419可能为通常CD20阴性的B细胞白血病提供治疗选择。

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