Sabbah Mohamad, Jondreville Ludovic, Lacan Claire, Norol Francoise, Vieillard Vincent, Roos-Weil Damien, Nguyen Stéphanie
Hematology Department, Pitie-Salpetriere Hospital, 75013 Paris, France.
Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Université, Inserm U1135, CNRS ERL 8255, 75013 Paris, France.
Cancers (Basel). 2022 Aug 8;14(15):3839. doi: 10.3390/cancers14153839.
Immunotherapy with chimeric antigen receptor-engineered T cells (CAR-T) has revolutionized the treatment landscape of relapsed/refractory B-cell malignancies. Nonetheless, the use of autologous T cells has certain limitations, including the variable quality and quantity of collected effector T cells, extended time of cell processing, limited number of available CAR cells, toxicities, and a high cost. Thanks to their powerful cytotoxic capabilities, with proven antitumor effects in both haploidentical hematopoietic stem cell transplantation and adoptive cell therapy against solid tumors and hematological malignancies, Natural Killer cells could be a promising alternative. Different sources of NK cells can be used, including cellular lines, cord blood, peripheral blood, and induced pluripotent stem cells. Their biggest advantage is the possibility of using them in an allogeneic context without major toxic side effects. However, the majority of the reports on CAR-NK cells concern preclinical or early clinical trials. Indeed, NK cells might be more difficult to engineer, and the optimization and standardization of expansion and transfection protocols need to be defined. Furthermore, their short persistence after infusion is also a major setback. However, with recent advances in manufacturing engineered CAR-NK cells exploiting their cytolytic capacities, antibody-dependent cellular cytotoxicity (ADCC), and cytokine production, "off-the-shelf" allogeneic CAR-NK cells can provide a great potential in cancer treatments.
嵌合抗原受体工程化T细胞(CAR-T)免疫疗法彻底改变了复发/难治性B细胞恶性肿瘤的治疗格局。尽管如此,自体T细胞的使用存在一定局限性,包括收集到的效应T细胞质量和数量参差不齐、细胞处理时间延长、可用的CAR细胞数量有限、毒性以及成本高昂。自然杀伤细胞凭借其强大的细胞毒性能力,在单倍体造血干细胞移植以及针对实体瘤和血液系统恶性肿瘤的过继性细胞治疗中均已证实具有抗肿瘤作用,可能是一种很有前景的替代方案。可使用不同来源的自然杀伤细胞,包括细胞系、脐带血、外周血和诱导多能干细胞。它们最大的优势在于有可能在同种异体环境中使用,且无重大毒副作用。然而,关于CAR-NK细胞的大多数报道都涉及临床前或早期临床试验。事实上,自然杀伤细胞可能更难进行工程改造,需要确定其扩增和转染方案的优化与标准化。此外,它们在输注后的短暂存活时间也是一个重大挫折。不过,随着利用自然杀伤细胞的细胞溶解能力、抗体依赖性细胞毒性(ADCC)和细胞因子产生来制造工程化CAR-NK细胞的技术取得了最新进展,“现货”型同种异体CAR-NK细胞在癌症治疗中具有巨大潜力。
Cancers (Basel). 2022-8-8
Stem Cell Res Ther. 2021-7-2
Stem Cells Transl Med. 2021-11
Am J Cancer Res. 2021-4-15
Immunother Adv. 2022-2-3
Rinsho Ketsueki. 2024
Front Immunol. 2025-7-17
Front Immunol. 2025-5-29
Front Immunol. 2025-3-13
Int J Nanomedicine. 2025-3-17
J Transl Med. 2025-1-22
Front Immunol. 2024-12-23
Chin Med J (Engl). 2024-11-5
Int J Cancer. 2025-1-15
Blood Cancer J. 2021-8-14
Mol Ther Methods Clin Dev. 2021-1-20
Hematology Am Soc Hematol Educ Program. 2020-12-4
Adv Exp Med Biol. 2020