Department of Hematology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Front Immunol. 2021 Jun 23;12:681984. doi: 10.3389/fimmu.2021.681984. eCollection 2021.
Non-Hodgkin's lymphoma (NHL) is a cancer that starts in the lymphatic system. In NHL, the important part of the immune system, a type of white blood cells called lymphocytes become cancerous. NHL subtypes include marginal zone lymphoma, small lymphocytic lymphoma, follicular lymphoma (FL), and lymphoplasmacytic lymphoma. The disease can emerge in either aggressive or indolent form. 5-year survival duration after diagnosis is poor among patients with aggressive/relapsing form of NHL. Therefore, it is necessary to understand the molecular mechanisms of pathogenesis involved in NHL establishment and progression. In the next step, we can develop innovative therapies for NHL based on our knowledge in signaling pathways, surface antigens, and tumor milieu of NHL. In the recent few decades, several treatment solutions of NHL mainly based on targeted/directed therapies have been evaluated. These approaches include B-cell receptor (BCR) signaling inhibitors, immunomodulatory agents, monoclonal antibodies (mAbs), epigenetic modulators, Bcl-2 inhibitors, checkpoint inhibitors, and T-cell therapy. In recent years, methods based on T cell immunotherapy have been considered as a novel promising anti-cancer strategy in the treatment of various types of cancers, and particularly in blood cancers. These methods could significantly increase the capacity of the immune system to induce durable anti-cancer responses in patients with chemotherapy-resistant lymphoma. One of the promising therapy methods involved in the triumph of immunotherapy is the chimeric antigen receptor (CAR) T cells with dramatically improved killing activity against tumor cells. The CAR-T cell-based anti-cancer therapy targeting a pan-B-cell marker, CD19 is recently approved by the US Food and Drug Administration (FDA) for the treatment of chemotherapy-resistant B-cell NHL. In this review, we will discuss the structure, molecular mechanisms, results of clinical trials, and the toxicity of CAR-T cell-based therapies. Also, we will criticize the clinical aspects, the treatment considerations, and the challenges and possible drawbacks of the application of CAR-T cells in the treatment of NHL.
非霍奇金淋巴瘤（NHL）是一种起源于淋巴系统的癌症。在 NHL 中，免疫系统的重要组成部分，即一种称为淋巴细胞的白细胞发生癌变。NHL 亚型包括边缘区淋巴瘤、小淋巴细胞淋巴瘤、滤泡性淋巴瘤（FL）和淋巴浆细胞淋巴瘤。该疾病可表现为侵袭性或惰性形式。患有侵袭性/复发性 NHL 形式的患者，其诊断后 5 年生存率较差。因此，有必要了解 NHL 发病机制中涉及的分子机制。在此基础上，我们可以根据 NHL 信号通路、表面抗原和肿瘤微环境方面的知识，为 NHL 开发创新疗法。在过去的几十年中，已经评估了几种基于 NHL 靶向/定向治疗的治疗方案。这些方法包括 B 细胞受体（BCR）信号抑制剂、免疫调节剂、单克隆抗体（mAb）、表观遗传调节剂、Bcl-2 抑制剂、检查点抑制剂和 T 细胞疗法。近年来，基于 T 细胞免疫疗法的方法已被认为是治疗各种类型癌症（尤其是血液癌症）的一种有前途的新型抗癌策略。这些方法可以显著提高免疫系统的能力，使化疗耐药淋巴瘤患者产生持久的抗癌反应。免疫疗法成功的一种有前途的治疗方法是嵌合抗原受体（CAR）T 细胞，它对肿瘤细胞具有显著提高的杀伤活性。靶向 pan-B 细胞标志物 CD19 的 CAR-T 细胞抗癌疗法最近已被美国食品和药物管理局（FDA）批准用于治疗化疗耐药 B 细胞 NHL。在这篇综述中，我们将讨论 CAR-T 细胞治疗的结构、分子机制、临床试验结果和毒性。此外，我们还将批评 CAR-T 细胞在 NHL 治疗中的临床应用的各个方面、治疗注意事项、挑战和可能的缺点。
