研究动态
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CAR T 细胞和化疗组合的治疗优势。

Therapeutic advantage of combinatorial CAR T cell and chemo-therapies.

发表日期:2024 Oct 07
作者: Meghan B Ward, Amber B Jones, Giedre Krenciute
来源: PHARMACOLOGICAL REVIEWS

摘要:

嵌合抗原受体 (CAR) T 细胞疗法改变了许多血液恶性肿瘤患者的治疗结果。然而,一些患者对 CAR T 细胞治疗没有反应,并且将 CAR T 细胞用于实体瘤和脑肿瘤已遇到许多挑战,包括恶劣的肿瘤微环境和较差的 CAR T 细胞持久性。因此,单独的 CAR T 细胞疗法不太可能足以在癌症患者中实现一致、完全的肿瘤清除。 CAR T 细胞和化疗药物的组合疗法是克服这一问题的一种有前途的方法,因为化疗药物可以增强 CAR T 细胞以提高抗肿瘤活性,或与 CAR T 细胞协同作用以清除肿瘤。在此,我们回顾了为实现成功的 CAR T 细胞和化学药物联合疗法所做的努力。我们专注于与已批准的化疗药物的联合疗法,因为这些药物将更容易转化为临床,但我们也会审查未经批准的化疗药物和药物筛选,旨在揭示有前途的新型 CAR T 细胞和化学药物组合。总之,这篇综述强调了 CAR T 细胞和化疗组合的前景,特别关注组合疗法如何克服单一疗法所面临的挑战,并支持这种治疗策略改善癌症患者预后的潜力。意义声明 通过与化疗药物的联合治疗来改善现有的 CAR T 细胞产品,有可能大幅增加癌症类型和可以从这些疗法中受益的患者数量,而单独使用这些疗法都不足以实现肿瘤清除。在此,我们对当前 CAR T 和化疗组合疗法的研究工作进行了全面回顾,并就未来识别新的有效组合的最佳方法提供了观点。
Chimeric antigen receptor (CAR) T cell therapies have transformed outcomes for many patients with hematological malignancies. However, some patients do not respond to CAR T cell treatment, and adapting CAR T cells for solid and brain tumors has been met with many challenges including a hostile tumor microenvironment and poor CAR T cell persistence. Thus, it is unlikely that CAR T cell therapy alone will be sufficient for consistent, complete tumor clearance across cancer patients. Combinatorial therapies of CAR T cells and chemotherapeutics are a promising approach for overcoming this as chemotherapeutics could augment CAR T cells for improved anti-tumor activity or work in tandem with CAR T cells to clear tumors. Herein, we review efforts towards achieving successful CAR T cell and chemical drug combination therapies. We focus on combination therapies with approved chemotherapeutics as these will be more easily translated to the clinic, but also review non-approved chemotherapeutics and drug screens designed to reveal promising new CAR T cell and chemical drug combinations. Together, this review highlights the promise of CAR T cell and chemotherapy combinations with specific focus on how combinatorial therapy overcomes challenges faced by either monotherapy and supports the potential of this therapeutic strategy to improve outcomes for cancer patients. Significance Statement Improving currently available CAR T cell products via combinatorial therapy with chemotherapeutics has the potential to drastically expand the types of cancers and number of patients that could benefit from these therapies when neither alone has been sufficient to achieve tumor clearance. Herein, we provide a thorough review of the current efforts towards studying CAR T and chemotherapy combinatorial therapies and provide perspectives on optimal ways to identify new and effective combinations moving forward.