Haploidentical hematopoietic cell transplantation as a platform for natural killer cell immunotherapy,American Journal of Hematology

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Haploidentical hematopoietic cell transplantation as a platform for natural killer cell immunotherapy
American Journal of Hematology ( IF 10.1 ) Pub Date : 2024-09-09 , DOI: 10.1002/ajh.27471
Rémy Duléry ₁ , Sara Piccinelli ₁ , Mohmad Shahnawaz Beg ₂ , Ji Eun Jang _{1,

3} , Rizwan Romee ₁

Affiliation

An innovative approach is crucially needed to manage relapse after allogeneic hematopoietic cell transplantation (HCT) in patients with advanced hematological malignancies. This review explores key aspects of haploidentical HCT with post-transplant cyclophosphamide, highlighting the potential and suitability of this platform for natural killer (NK) cell immunotherapy. NK cells, known for their unique abilities to eliminate cancer cells, can also exhibit memory-like features and enhanced cytotoxicity when activated by cytokines. By discussing promising results from clinical trials, the review delves into the recent major advances: donor-derived NK cells can be expanded ex vivo in large numbers, cytokine activation may enhance NK cell persistence and efficacy in vivo, and post-HCT NK cell infusion can improve outcomes in high-risk and/or relapsed myeloid malignancies without increasing the risk of graft-versus-host disease, severe cytokine release syndrome, or neurotoxicity. Looking ahead, cytokine-activated NK cells can be synergized with immunomodulatory agents and/or genetically engineered to enhance their tumor-targeting specificity, cytotoxicity, and persistence while preventing exhaustion. The ongoing exploration of these strategies holds promising preliminary results and could be rapidly translated into clinical applications for the benefit of the patients.

中文翻译：

单倍体造血细胞移植作为自然杀伤细胞免疫治疗的平台

对于晚期血液系统恶性肿瘤患者，迫切需要一种创新方法来管理同种异体造血细胞移植（HCT）后的复发。本文探讨了移植后环磷酰胺半相合 HCT 的关键方面，强调了该平台在自然杀伤（NK）细胞免疫治疗中的潜力和适用性。NK 细胞以其消除癌细胞的独特能力而闻名，当被细胞因子激活时，也会表现出类似记忆的特征和增强的细胞毒性。通过讨论临床试验的有希望的结果，本综述深入探讨了最近的主要进展：供体来源的 NK 细胞可以在体外大量扩增，细胞因子激活可能会增强 NK 细胞在体内的持久性和疗效，HCT 后 NK 细胞输注可以改善高危和/或复发性髓系恶性肿瘤的预后，而不会增加移植物抗宿主病的风险，严重的细胞因子释放综合征或神经毒性。展望未来，细胞因子激活的 NK 细胞可以与免疫调节剂协同作用和/或进行基因工程改造，以增强其肿瘤靶向特异性、细胞毒性和持久性，同时防止耗竭。对这些策略的持续探索取得了有希望的初步结果，并且可以迅速转化为临床应用，造福患者。

更新日期：2024-09-09

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