Development of BCMA-Targeted Bispecific Natural Killer Cell Engagers for Multiple Myeloma Treatment.

IF 2.7 Q3 IMMUNOLOGY

Antibodies Pub Date : 2024-11-29 DOI:10.3390/antib13040097

Minchuan Zhang, Han Ping Loh, Shiyi Goh Fang, Yuansheng Yang, Kong-Peng Lam, Shengli Xu

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引用次数: 0

Abstract

Background: B-cell maturation antigen (BCMA)-targeted T cell-redirecting immunotherapies, including Chimeric Antigen Receptor (CAR) T-cell therapy and T-cell engagers have demonstrated remarkable success in treating relapsed/refractory (RR) multiple myeloma (MM), a malignancy of plasma cells. However, a significant challenge is the severe side effects associated with T-cell overactivation, leading to cytokine release syndrome and neurotoxicity in MM patients undergoing such therapies. Bispecific NK cell engagers (NKCEs) may offer a promising alternative by redirecting NK cell cytotoxic activity towards tumor cells without triggering cytokine release syndrome.

Methods: In this study, we designed a series of BCMA × CD16 NKCEs that simultaneously engage BCMA and CD16 on MM and NK cells, respectively. We evaluated the functionality of these NKCEs in vitro with respect to their molecular design.

Results: Our results indicate that the format design of NKCEs influences their functionalities, underscoring the importance of format selection in optimizing NKCE-based therapies for MM. This study provides valuable insights for developing next-generation NKCEs and advancing therapeutic strategies for MM and potentially other malignancies.

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bcma靶向双特异性自然杀伤细胞接合物治疗多发性骨髓瘤的研究进展。

背景：b细胞成熟抗原（BCMA）靶向T细胞重定向免疫疗法，包括嵌合抗原受体（CAR） T细胞疗法和T细胞接合物在治疗复发/难治性（RR）多发性骨髓瘤（MM）方面取得了显著成功，多发性骨髓瘤是一种恶性浆细胞。然而，一个重大的挑战是与t细胞过度激活相关的严重副作用，导致接受此类治疗的MM患者的细胞因子释放综合征和神经毒性。双特异性NK细胞参与物（NKCEs）可能提供了一种有希望的替代方法，它可以将NK细胞的细胞毒活性重定向到肿瘤细胞，而不会引发细胞因子释放综合征。方法：在本研究中，我们设计了一系列BCMA × CD16 nkce，分别在MM细胞和NK细胞上同时作用BCMA和CD16。我们在体外评估了这些nkce的分子设计功能。结果：我们的研究结果表明，nkce的格式设计影响其功能，强调了格式选择在优化基于nkce的MM治疗中的重要性。这项研究为开发下一代nkce和推进MM和潜在的其他恶性肿瘤的治疗策略提供了有价值的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Antibodies IMMUNOLOGY-

CiteScore

7.10

自引率

6.40%

发文量

审稿时长

11 weeks

期刊介绍： Antibodies (ISSN 2073-4468), an international, peer-reviewed open access journal which provides an advanced forum for studies related to antibodies and antigens. It publishes reviews, research articles, communications and short notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. Full experimental and/or methodical details must be provided. Electronic files or software regarding the full details of the calculation and experimental procedure - if unable to be published in a normal way - can be deposited as supplementary material. This journal covers all topics related to antibodies and antigens, topics of interest include (but are not limited to): antibody-producing cells (including B cells), antibody structure and function, antibody-antigen interactions, Fc receptors, antibody manufacturing antibody engineering, antibody therapy, immunoassays, antibody diagnosis, tissue antigens, exogenous antigens, endogenous antigens, autoantigens, monoclonal antibodies, natural antibodies, humoral immune responses, immunoregulatory molecules.