肿瘤细胞治疗研究
英文原题：A tetraspecific engager armed with a non-alpha IL-2 variant harnesses natural killer cells against B cell non-Hodgkin lymphoma.
A tetraspecific engager armed with a non-alpha IL-2 variant harnesses natural killer cells against B cell non-Hodgkin lymphoma.
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NK 细胞为肿瘤中的 T 细胞疗法提供了一种有前景的替代选择。
NK细胞为癌症治疗提供了T细胞疗法之外的有前景替代选择。我们评估了IPH6501，这是一种临床阶段的四特异性NK细胞衔接器（NKCE），携带非α型IL-2变体（IL-2v），靶向CD20，开发用于治疗B细胞非霍奇金淋巴瘤（B-NHL）。CD20-NKCE-IL2v可增强NK细胞增殖和细胞毒性，对包括CD20密度较低细胞在内的多种B-NHL细胞系均有活性。与T细胞疗法常见毒性相比，CD20-NKCE-IL2v毒性较低；在体外临床前模型中，其杀伤效力高于靶向CD20的T细胞衔接器。CD20-NKCE-IL2v还提高NK细胞表面活化受体表达，使其能够攻击CD20阴性肿瘤细胞。非人灵长类动物和肿瘤小鼠模型中的体内研究进一步验证了其疗效，并显示CD20-NKCE-IL2v可诱导外周NK细胞归巢至肿瘤部位。CD20-NKCE-IL2v有望成为B-NHL治疗格局中的一种替代方案。
NK cells offer a promising alternative to T cell therapies in cancer. We evaluated IPH6501, a clinical-stage, tetraspecific NK cell engager (NKCE) armed with a non-alpha IL-2 variant (IL-2v), which targets CD20 and was developed for treating B cell non-Hodgkin lymphoma (B-NHL). CD20-NKCE-IL2v boosts NK cell proliferation and cytotoxicity, showing activity against a range of B-NHL cell lines, including those with low CD20 density. Whereas it presented reduced toxicities compared with those commonly associated with T cell therapies, CD20-NKCE-IL2v showed greater killing efficacy over a T cell engager targeting CD20 in in vitro preclinical models. CD20-NKCE-IL2v also increased the cell surface expression of NK cell-activating receptors, leading to activity against CD20-negative tumor cells. In vivo studies in nonhuman primates and tumor mouse models further validated its efficacy and revealed that CD20-NKCE-IL2v induces peripheral NK cell homing at the tumor site. CD20-NKCE-IL2v emerges as a potential alternative in the treatment landscape of B-NHL.
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