CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Gamma/delta T cells as cellular vehicles for anti-tumor immunity.
Gamma/delta T cells as cellular vehicles for anti-tumor immunity.
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过继性细胞免疫治疗作为治疗癌症的新范式,其代表性成果是近年来FDA批准了六种靶向血液系统恶性肿瘤的CAR-T 细胞疗法。这些疗法中应用的常规αβ T细胞已被证明有效,但几乎仅限于自体使用。当输注到人类白细胞抗原不匹配的患者体内时,αβ T细胞会将该患者的组织识别为异物,并引发毁灭性的移植物抗宿主病。
因此,克服这一挑战的一种方法是使用天然同种异体免疫细胞类型,如γδ T细胞。γδ T细胞占据固有免疫与适应性免疫之间的界面,具有检测转化宿主细胞上多种配体的能力。在本文中,我们综述了γδ T细胞的基础生物学,包括其亚型、配体表达、在癌症预后或生存中的对比作用及关联,并讨论了目前我们致力于阐明的关于该细胞类型的知识空白。
此外,我们基于从既往临床试验中汲取的经验教训,提出如何利用γδ T细胞的独特特性进行细胞免疫治疗,并提供涉及这些细胞的正在进行试验的最新进展。
最后,我们阐述了已测试或可探索的用于提高γδ T细胞体内抗肿瘤活性与持久性的策略。
Adoptive cellular immunotherapy as a new paradigm to treat cancers is exemplified by the FDA approval of six chimeric antigen receptor-T cell therapies targeting hematological malignancies in recent years. Conventional αβ T cells applied in these therapies have proven efficacy but are confined almost exclusively to autologous use. When infused into patients with mismatched human leukocyte antigen, αβ T cells recognize tissues of such patients as foreign and elicit devastating graft-versus-host disease.
Therefore, one way to overcome this challenge is to use naturally allogeneic immune cell types, such as γδ T cells. γδ T cells occupy the interface between innate and adaptive immunity and possess the capacity to detect a wide variety of ligands on transformed host cells.
In this article, we review the fundamental biology of γδ T cells, including their subtypes, expression of ligands, contrasting roles in and association with cancer prognosis or survival, as well as discuss the gaps in knowledge pertaining to this cell type which we currently endeavor to elucidate.
In addition, we propose how to harness the unique properties of γδ T cells for cellular immunotherapy based on lessons gleaned from past clinical trials and provide an update on ongoing trials involving these cells. Lastly, we elaborate strategies that have been tested or can be explored to improve the anti-tumor activity and durability of γδ T cells in vivo .
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