Interactions with the Environment Program, Immune System Development and Function Unit, Centro de Biología Molecular Severo Ochoa, CSIC-UAM, 28049 Madrid, Spain.
Int J Mol Sci. 2020 Oct 16;21(20):7685. doi: 10.3390/ijms21207685.
T-cell acute lymphoblastic leukemia (T-ALL), a T-cell malignant disease that mainly affects children, is still a medical challenge, especially for refractory patients for whom therapeutic options are scarce. Recent advances in immunotherapy for B-cell malignancies based on increasingly efficacious monoclonal antibodies (mAbs) and chimeric antigen receptors (CARs) have been encouraging for non-responding or relapsing patients suffering from other aggressive cancers like T-ALL. However, secondary life-threatening T-cell immunodeficiency due to shared expression of targeted antigens by healthy and malignant T cells is a main drawback of mAb-or CAR-based immunotherapies for T-ALL and other T-cell malignancies. This review provides a comprehensive update on the different immunotherapeutic strategies that are being currently applied to T-ALL. We highlight recent progress on the identification of new potential targets showing promising preclinical results and discuss current challenges and opportunities for developing novel safe and efficacious immunotherapies for T-ALL.
T 细胞急性淋巴细胞白血病(T-ALL)是一种主要影响儿童的 T 细胞恶性疾病,仍然是一个医学挑战,特别是对于那些难治性患者,他们的治疗选择很少。基于越来越有效的单克隆抗体(mAbs)和嵌合抗原受体(CARs)的 B 细胞恶性肿瘤免疫治疗的最新进展,对于其他侵袭性癌症(如 T-ALL)的无反应或复发患者来说是令人鼓舞的。然而,由于健康和恶性 T 细胞共同表达靶向抗原,导致继发的危及生命的 T 细胞免疫缺陷,这是 mAb 或 CAR 为基础的 T-ALL 和其他 T 细胞恶性肿瘤免疫治疗的一个主要缺点。这篇综述提供了目前应用于 T-ALL 的不同免疫治疗策略的全面更新。我们强调了在鉴定新的潜在靶标方面的最新进展,这些靶标具有有前景的临床前结果,并讨论了为 T-ALL 开发新型安全有效的免疫疗法的当前挑战和机遇。