癌症免疫治疗中的新兴先天免疫细胞:前景与挑战。

Emerging Innate Immune Cells in Cancer Immunotherapy: Promises and Challenges.

机构信息

Department of Urology, Feinberg School of Medicine, Robert Lurie Comprehensive Cancer Center, Northwestern University, 303 E. Superior St, Chicago, IL, 60611, USA.

Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

出版信息

BioDrugs. 2024 Jul;38(4):499-509. doi: 10.1007/s40259-024-00657-2. Epub 2024 May 3.

Abstract

Immune checkpoint inhibitor (ICI)-based therapy has made an unprecedented impact on survival benefit for a subset of cancer patients; however, only a subset of cancer patients is benefiting from ICI therapy if all cancer types are considered. With the advanced understanding of interactions of immune effector cell types and tumors, cell-based therapies are emerging as alternatives to patients who could not benefit from ICI therapy. Pioneering work of chimeric antigen receptor T (CAR-T) therapy for hematological malignancies has brought encouragement to a broad range of development for cellular-based cancer immunotherapy, both innate immune cell-based therapies and T-cell-based therapies. Innate immune cells are important cell types due to their rapid response, versatile function, superior safety profiles being demonstrated in early clinical development, and being able to utilize multiple allogeneic cell sources. Efforts on engineering innate immune cells and exploring their therapeutic potential are rapidly emerging. Some of the therapies, such as CD19 CAR natural killer (CAR-NK) cell-based therapy, have demonstrated comparable early efficacy with CD19 CAR-T cells. These studies underscore the significance of developing innate immune cells for cancer therapy. In this review, we focus on the current development of emerging NK cells, γδ T cells, and macrophages. We also present our views on potential challenges and perspectives to overcome these challenges.

摘要

免疫检查点抑制剂(ICI)治疗在一定程度上提高了部分癌症患者的生存获益,但如果考虑所有癌症类型,只有一部分癌症患者能从 ICI 治疗中获益。随着对免疫效应细胞类型与肿瘤相互作用的深入了解,细胞疗法正成为不能从 ICI 治疗中获益的患者的替代疗法。嵌合抗原受体 T(CAR-T)疗法在血液恶性肿瘤方面的开创性工作为广泛开发基于细胞的癌症免疫疗法,包括固有免疫细胞疗法和 T 细胞疗法,带来了鼓舞。固有免疫细胞是重要的细胞类型,因为它们具有快速反应、多功能、在早期临床开发中显示出优越的安全性特征,并且能够利用多种同种异体细胞来源。目前正在迅速开展对固有免疫细胞进行工程改造和探索其治疗潜力的工作。一些疗法,如 CD19 CAR 自然杀伤(CAR-NK)细胞疗法,已经显示出与 CD19 CAR-T 细胞相当的早期疗效。这些研究强调了开发用于癌症治疗的固有免疫细胞的重要性。在这篇综述中,我们重点介绍新兴 NK 细胞、γδ T 细胞和巨噬细胞的最新发展。我们还提出了对潜在挑战的看法以及克服这些挑战的观点。

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