ABSTRACT

Introduction

Despite advances in modern evidence-based medicine, cancer remains a major cause of global disease-associated mortality. CAR T-cell therapy is a major histocompatibility complex (MHC)-independent immunotherapy involving adoptive cell transfer. Cancer immunotherapy witnessed a major breakthrough with the US FDA approval of the first chimeric antigen receptor (CAR) T-cell therapy Kymriah^TM (tisagenlecleucel) for relapsed or refractory (R/R) acute lymphoblastic leukemia (ALL) in August 2017 followed by approval of Yescarta® (axicabtagene ciloleucel) for R/R non-Hodgkin’s lymphoma (NHL) in October 2017.

Areas covered

We review the potential of CAR T-cell therapy which, despite showing great promise in hematological malignancies, faces significant challenges in targeting solid tumors. We address these challenges and discuss proposed strategies to overcome them in solid tumors. We highlight the potential of CAR T-cell therapy as cancer precision medicine and briefly discuss the ‘financial toxicity’ of CAR T-cell therapy.

Expert opinion

Taken together, we discuss various strategies to circumvent the limitations of CAR T-cell therapy in solid tumors. Despite the rapid advances in CAR NK-cell therapies, there is immense scope for CAR T-cell therapy in solid tumors. We provide a synthetic review of CAR T-cell therapy that will drive future research and harness its full potential in cancer precision medicine for solid tumors.

中文翻译：

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CAR T 细胞疗法的新前景：实体瘤的挑战和机遇

摘要

介绍

尽管现代循证医学取得了进步，但癌症仍然是全球疾病相关死亡的主要原因。CAR T 细胞疗法是一种主要的组织相容性复合体 (MHC) 独立免疫疗法，涉及过继细胞转移。2017 年 8 月，美国 FDA 批准首个用于治疗复发或难治性（R/R）急性淋巴细胞白血病（ALL）的嵌合抗原受体（CAR）T 细胞疗法 Kymriah ^TM（tisagenlecleucel），癌症免疫疗法取得重大突破，随后获批Yescarta® (axicabtagene ciloleucel) 于 2017 年 10 月用于 R/R 非霍奇金淋巴瘤 (NHL)。

覆盖区域

我们回顾了 CAR T 细胞疗法的潜力，尽管它在血液系统恶性肿瘤中显示出巨大的前景，但在靶向实体瘤方面面临着重大挑战。我们应对这些挑战并讨论在实体瘤中克服这些挑战的拟议策略。我们强调了 CAR T 细胞疗法作为癌症精准医学的潜力，并简要讨论了 CAR T 细胞疗法的“财务毒性”。

专家意见

总之，我们讨论了各种策略来规避 CAR T 细胞疗法在实体瘤中的局限性。尽管 CAR NK 细胞疗法取得了快速进展，但 CAR T 细胞疗法在实体瘤中仍有巨大的发展空间。我们提供了对 CAR T 细胞疗法的综合评价，这将推动未来的研究，并利用其在实体瘤癌症精准医学中的全部潜力。