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通过协同联合方案的共同应用增强 CAR-T 细胞疗法

英文原题:Enhanced Chimeric Antigen Receptor T Cell Therapy through Co-Application of Synergistic Combination Partners.

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Enhanced Chimeric Antigen Receptor T Cell Therapy through Co-Application of Synergistic Combination Partners.

PubMed 2022/01/28(内容时间) Biomedicines Q2 · IF 4.5(JCR 2025)

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中文摘要

嵌合抗原受体(CAR)T细胞疗法已取得显著的缓解率,并彻底改变了特定血液系统恶性肿瘤患者的治疗格局。然而,许多患者仍然对该疗法无应答或在初始缓解后复发,这凸显了提高疗效的必要性。CAR-T 细胞体内活性、持久性、迁移和肿瘤浸润不足,以及抗原逃逸和治疗相关不良事件,限制了治疗的成功。目前已研究多种策略和方法以进一步改进CAR-T 细胞疗法。除对CAR本身进行基因修饰外,与其他治疗方式的联合也有潜力改善这一方法。特别是,将CAR-T 细胞与临床已批准的化合物(如单克隆抗体和小分子抑制剂)联合可能是一种有前景的策略。联合伙伴甚至可以在生产过程中应用,以影响最终CAR-T 细胞产品的细胞组成和免疫表型。或者,将临床已批准的化合物与CAR-T 细胞同时给药将是另一条可行的途径。在本综述中,我们将讨论当前将CAR-T 细胞与化合物联合的策略,以克服近期的局限性并进一步增强这一有前景的癌症疗法, potentially broadening its application beyond hematology.

展开英文摘要原文

Chimeric antigen receptor (CAR) T cell therapy has achieved remarkable response rates and revolutionized the treatment of patients suffering from defined hematological malignancies.

However, many patients still do not respond to this therapy or relapse after an initial remission, underscoring the need for improved efficacy. Insufficient in vivo activity, persistence, trafficking, and tumor infiltration of CAR T cells, as well as antigen escape and treatment-associated adverse events, limit the therapeutic success. Multiple strategies and approaches have been investigated to further improve CAR T cell therapy. Besides genetic modification of the CAR itself, the combination with other treatment modalities has the potential to improve this approach.

In particular, combining CAR T cells with clinically approved compounds such as monoclonal antibodies and small molecule inhibitors might be a promising strategy. Combination partners could already be applied during the production process to influence the cellular composition and immunophenotype of the final CAR T cell product.

Alternatively, simultaneous administration of clinically approved compounds with CAR T cells would be another feasible avenue. In this review, we will discuss current strategies to combine CAR T cells with compounds to overcome recent limitations and further enhance this promising cancer therapy, potentially broadening its application beyond hematology.

论文信息

作者
Stock S、Kluever AK、Endres S、Kobold S
单位
Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig Maximilian University (LMU) of Munich, 80337 Munich, Germany.Germany
文献类型
综述
期刊
Biomedicines2022 Jan 28
原文标识
PubMed 35203517 · DOI 10.3390/biomedicines10020307