NK92 cells stably transfected with CD16 are efficient against multiple myeloma cells ex vivo and in vivo, especially if combined with daratumumab.

IF 6.5 2区 医学 Q1 IMMUNOLOGY
Oncoimmunology Pub Date : 2025-12-01 Epub Date: 2025-09-25 DOI:10.1080/2162402X.2025.2559782
David Giraldos, Evelyn Galano-Frutos, Laura Cambronero-Arregui, Manuel Beltrán Visiedo, Eduardo Romanos, Chantal Reina-Ortiz, Gemma Azaceta, Beatriz Martínez-Lázaro, Bárbara Menéndez-Jándula, Alejandro García-Romero, Francisco Javier Jiménez-Albericio, Isabel Marzo, Javier Naval, Alberto Anel
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引用次数: 0

Abstract

Adoptive cell therapy and the use of monoclonal antibodies are two therapeutic modalities implemented in the treatment of multiple myeloma (MM). In this study, we combined the anti-CD38 therapeutic mAb daratumumab with different types of NK cells, leveraging the antibody-dependent cell-mediated cytotoxicity (ADCC) performed by these immune cells. Daratumumab was initially combined with activated and expanded NK cells (eNK), resulting in significant cytotoxic activity against human MM cell lines. As an alternative model to minimize the variability among donors of NK cells, the NK92 cell line was used, which showed greater cytotoxic activity than eNK cells against MM cell lines. However, since NK92 cells lacked CD16 receptor expression, they could not be used in combination with mAbs. To circumvent this, we performed a CD16 transfection on NK92 cells, generating the stable NK92-CD16 cell line. These cells were tested in combination with daratumumab against human MM cell lines with excellent results under various conditions, such as 2D and 3D cultures, even at very low effector-to-target ratios. NK92-CD16 cells were then tested in the presence of daratumumab against plasma cells from MM patients, with anti-myeloma activity even against cells from relapsed patients. In vivo experiments using MM xenografts or intravenous injection of MM cells in NGS mice, followed by treatment with NK92-CD16 cells in the presence or absence of daratumumab showed tumor regressions, especially in the second model, with nearly complete elimination of the MM cells when NK92-CD16 cells were combined with daratumumab.

稳定转染CD16的NK92细胞在体内和体外对多发性骨髓瘤细胞有效,特别是如果与daratumumab联合使用。
过继细胞疗法和单克隆抗体的使用是治疗多发性骨髓瘤(MM)的两种治疗方式。在这项研究中,我们将抗cd38治疗性单抗daratumumab与不同类型的NK细胞联合使用,利用这些免疫细胞执行的抗体依赖性细胞介导的细胞毒性(ADCC)。Daratumumab最初与活化和扩增的NK细胞(eNK)联合使用,对人MM细胞系产生显著的细胞毒活性。作为最小化NK细胞供体差异性的替代模型,研究人员使用了NK92细胞系,其对MM细胞系的细胞毒活性比eNK细胞更强。然而,由于NK92细胞缺乏CD16受体的表达,它们不能与单克隆抗体联合使用。为了避免这种情况,我们在NK92细胞上进行了CD16转染,产生了稳定的NK92-CD16细胞系。这些细胞与daratumumab联合对人MM细胞系进行了测试,在各种条件下,例如2D和3D培养,即使在非常低的效靶比下,也取得了出色的结果。然后在daratumumab存在下测试NK92-CD16细胞对MM患者浆细胞的作用,甚至对复发患者的细胞也具有抗骨髓瘤活性。在体内实验中,在NGS小鼠中使用MM异种移植或静脉注射MM细胞,然后在存在或不存在daratumumab的情况下使用NK92-CD16细胞治疗,结果显示肿瘤消退,特别是在第二种模型中,当NK92-CD16细胞与daratumumab联合使用时,MM细胞几乎完全消除。
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
Oncoimmunology
Oncoimmunology ONCOLOGYIMMUNOLOGY-IMMUNOLOGY
CiteScore
12.50
自引率
2.80%
发文量
276
审稿时长
24 weeks
期刊介绍: OncoImmunology is a dynamic, high-profile, open access journal that comprehensively covers tumor immunology and immunotherapy. As cancer immunotherapy advances, OncoImmunology is committed to publishing top-tier research encompassing all facets of basic and applied tumor immunology. The journal covers a wide range of topics, including: -Basic and translational studies in immunology of both solid and hematological malignancies -Inflammation, innate and acquired immune responses against cancer -Mechanisms of cancer immunoediting and immune evasion -Modern immunotherapies, including immunomodulators, immune checkpoint inhibitors, T-cell, NK-cell, and macrophage engagers, and CAR T cells -Immunological effects of conventional anticancer therapies.
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