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:Chimeric antigen receptor T-cell therapy in hematologic malignancies: Successes, challenges, and opportunities.
Chimeric antigen receptor T-cell therapy in hematologic malignancies: Successes, challenges, and opportunities.
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CAR-T 细胞疗法在血液系统恶性肿瘤中的成功,实现了长期以来利用免疫系统以真正个性化方式对抗癌症的努力。第二代嵌合抗原受体(CAR)整合了4-1BB或CD28等共刺激分子,能够克服初始CAR构建体的一些障碍,从而产生有效的产品。许多第二代CAR-T 产品已获批用于治疗复发/难治性血液系统恶性肿瘤,包括多发性骨髓瘤(MM)、非霍奇金淋巴瘤(NHL)和急性淋巴细胞白血病。然而,在优化生产、及时可及性、限制CAR-T 输注毒性以及提高CAR-T 疗法缓解持久性方面仍存在挑战。在此,我们总结了促成CAR-T 疗法在MM和NHL中获批的临床试验数据,讨论了当前CAR-T 治疗策略的局限性,并综述了克服这些局限性的新兴策略。
The success of chimeric antigen receptor T-cell (CAR-T) therapy in hematologic malignancies has realized a longstanding effort toward harnessing the immune system to fight cancer in a truly personalized fashion. Second generation chimeric antigen receptors (CAR) incorporating co-stimulatory molecules like 4-1BB or CD28 were able to overcome some of the hindrances with initial CAR constructs resulting in efficacious products.
Many second-generation CAR-T products have been approved in the treatment of relapsed/refractory hematologic malignancies including multiple myeloma (MM), non-Hodgkin lymphoma (NHL), and acute lymphoblastic leukemia.
However, challenges remain in optimizing the manufacturing, timely access, limiting the toxicity from CAR-T infusions and improving sustainability of responses derived with CAR-T therapy.
Here, we summarize the clinical trial data leading to approval CAR-T therapies in MM and NHL, discuss the limitations with current CAR-T therapy strategies and review emerging strategies for overcoming these limitations.
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