D'Avanzo Claudia, Blaeschke Franziska, Lysandrou Memnon, Ingelfinger Florian, Zeiser Robert
Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
German Cancer Research Center (DKFZ), Heidelberg, Germany; Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Heidelberg University Hospital, Heidelberg, Germany.
Trends Pharmacol Sci. 2024 Dec;45(12):1119-1134. doi: 10.1016/j.tips.2024.10.016. Epub 2024 Nov 27.
Cell-based therapies harness the endogenous ability of the immune system to fight cancer and have shown promising results in the treatment of hematological malignancies. However, their clinical application beyond B cell malignancies is hampered by numerous hurdles, ranging from relapsed disease to a hostile tumor microenvironment (TME). Recent advances in cell engineering and TME modulation may expand the applicability of these therapies to a wider range of cancers, creating new treatment possibilities. Breakthroughs in advanced gene editing and sophisticated cell engineering, have also provided promising solutions to longstanding challenges. In this review, we examine the challenges and future directions of the most prominent cell-based therapies, including chimeric antigen receptor (CAR)-T cells, tumor-infiltrating lymphocytes (TILs), and natural killer (NK) cells, and emerging modalities. We provide a comprehensive analysis of emerging cell types and combination strategies translated into clinical trials, offering insights into the next generation of cell-based cancer treatments.
基于细胞的疗法利用免疫系统对抗癌症的内在能力，并且在血液系统恶性肿瘤的治疗中已显示出有前景的结果。然而，它们在B细胞恶性肿瘤之外的临床应用受到众多障碍的阻碍，从疾病复发到不利的肿瘤微环境（TME）不等。细胞工程和TME调节方面的最新进展可能会将这些疗法的适用性扩展到更广泛的癌症类型，创造新的治疗可能性。先进基因编辑和精密细胞工程方面的突破，也为长期存在的挑战提供了有前景的解决方案。在这篇综述中，我们研究了最突出的基于细胞的疗法的挑战和未来方向，包括嵌合抗原受体（CAR）-T细胞、肿瘤浸润淋巴细胞（TILs）和自然杀伤（NK）细胞，以及新兴模式。我们对已转化为临床试验的新兴细胞类型和联合策略进行了全面分析，为下一代基于细胞的癌症治疗提供见解。
