“现成的”免疫疗法:多能干细胞衍生免疫细胞的生成与应用。
'Off the shelf' immunotherapies: Generation and application of pluripotent stem cell-derived immune cells.
发表日期:2023 Mar 01
作者:
Chenxin Wang, Jingjing Liu, Wei Li
来源:
CELL PROLIFERATION
摘要:
近年来,在治疗难治性恶性肿瘤方面,免疫细胞基因治疗方面已经取得了巨大的进步。带有嵌合抗原受体的原代T细胞和NK细胞特别是在白血病和淋巴瘤患者中取得了巨大的临床成功。然而,这些效应细胞的自体起源意味着,单一批量工程化细胞只能治疗某个特定的患者,导致高成本、产品质量不均匀以及延迟治疗的风险,因此限制了这些治疗方法对绝大多数患者的可及性。解决这些棘手的障碍需要发展出通用免疫细胞产品,这些产品可以提供大量的“现成品”。多能干细胞(PSCs)由于其自我更新的独特能力和多线性分化的潜力,为生成均匀且可扩展的工程免疫细胞提供了无限的细胞来源。本文综述了PSC源性免疫细胞分化途径的主要进展以及它们在治疗血液恶性肿瘤和实体肿瘤方面的治疗潜力。我们还考虑了PSC源性免疫细胞作为治疗其他疾病(如自身免疫性疾病、纤维化、感染等)的替代治疗策略的效力。© 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.
In recent years, great strides have been made toward the development of immune cell-based therapies in the treatment of refractory malignancies. Primary T cells and NK cells armed with chimeric antigen receptors have achieved tremendous clinical success especially in patients with leukaemia and lymphoma. However, the autologous origin of these effector cells means that a single batch of laboriously engineered cells treats only a certain patient, leading to high cost, ununiform product quality, and risk of delay in treatment, and therefore results in restricted accessibility of these therapies to the overwhelming majority of the patients. Addressing these tricky obstacles calls for the development of universal immune cell products that can be provided 'off the shelf' in a large amount. Pluripotent stem cells (PSCs), owing to their unique capacity of self-renewal and the potential of multi-lineage differentiation, offer an unlimited cell source to generate uniform and scalable engineered immune cells. This review discusses the major advances in the development of PSC-derived immune cell differentiation approaches and their therapeutic potential in treating both hematologic malignancies and solid tumours. We also consider the potency of PSC-derived immune cells as an alternative therapeutic strategy for other diseases, such as autoimmune diseases, fibrosis, infections, et al.© 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.