Chimeric antigen receptor (CAR) T cell therapy has been successful in treating B cell malignancies in clinical trials; however, fewer studies have evaluated CAR T cell therapy for the treatment of T cell malignancies. There are many challenges in translating this therapy for T cell disease, including fratricide, T cell aplasia, and product contamination. To the best of our knowledge, no tumor-specific antigen has been identified with universal expression on cancerous T cells, hindering CAR T cell therapy for these malignancies. Numerous approaches have been assessed to address each of these challenges, such as (i) disrupting target antigen expression on CAR-modified T cells, (ii) targeting antigens with limited expression on T cells, and (iii) using third party donor cells that are either non-alloreactive or have been genome edited at the T cell receptor α constant (TRAC) locus. In this review, we discuss CAR approaches that have been explored both in preclinical and clinical studies targeting T cell antigens, as well as examine other potential strategies that can be used to successfully translate this therapy for T cell disease.

中文翻译：

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使用基于 CAR 的免疫疗法靶向 T 细胞恶性肿瘤：挑战和潜在解决方案。


嵌合抗原受体（CAR）T细胞疗法在临床试验中已成功治疗B细胞恶性肿瘤；然而，评估 CAR T 细胞疗法治疗 T 细胞恶性肿瘤的研究较少。将这种疗法转化为 T 细胞疾病存在许多挑战，包括自相残杀、T 细胞再生障碍和产品污染。据我们所知，尚未发现在癌性 T 细胞上普遍表达的肿瘤特异性抗原，这阻碍了针对这些恶性肿瘤的 CAR T 细胞疗法。已经评估了许多方法来解决这些挑战，例如（i）破坏 CAR 修饰的 T 细胞上的靶抗原表达，（ii）靶向 T 细胞上表达有限的抗原，以及（iii）使用第三方供体细胞要么是非同种异体反应性，要么是在 T 细胞受体 α 恒定 (TRAC) 位点进行了基因组编辑。在这篇综述中，我们讨论了在针对 T 细胞抗原的临床前和临床研究中探索过的 CAR 方法，并研究了可用于成功转化这种 T 细胞疾病疗法的其他潜在策略。