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嵌合抗原受体T细胞疗法:抗癌斗争中的希望之光。

Chimeric Antigen Receptor T-Cell Therapy: A Beacon of Hope in the Fight Against Cancer.

作者信息

Tariq Syed Maaz, Haider Syed Ali, Hasan Mohammad, Tahir Amber, Khan Maria, Rehan Arisha, Kamal Anum

机构信息

Internal Medicine, Jinnah Sindh Medical University, Karachi, PAK.

Internal Medicine, Dow University of Health Sciences, Karachi, PAK.

出版信息

Cureus. 2018 Oct 23;10(10):e3486. doi: 10.7759/cureus.3486.

Abstract

Despite significant advancements, relapses, and persistent malignancies are still a major challenge faced by the oncologists. Immunotherapy has shown remarkable potential in induction of sustained remission in refractory malignancies. Chimeric antigen receptor T-cell (CAR-T) therapy is a newer treatment methodology approved by the Food and Drug Administration (FDA). The chimeric pairing of an antigen receptor with the T-cell receptor (TCR) intracellular signaling domain allows cluster of designation 8 (CD8) cytotoxic T-cells to target cell surface makers independent of major histocompatibility complex (MHC) activation. Another essential feature which contributes to the broad applicability of CARs and expanding their potential targets is their ability to bind not only to proteins but also to carbohydrate and glycolipid structures. Their antigen-specific and targeted immune responses have shown promising outcomes in clinical trials particularly involving B-cell malignancies and solid tumors. High remission rates and low percentages of relapses have caused a paradigm shift in the treatment of relapsed or refractory cancers. Challenges include side effects such as cytokine release syndrome, on-target off-tumor toxicities, and replication of its success in treating solid tumors. The burden of side effects and hefty cost of treatment are major obstacles which could hinder its progress globally. Nevertheless, ongoing research would only result in a maximized therapeutic potential in addition to more patient- and cost-friendly treatment. In this review, we aim to provide the readers an overview of chimeric antigen receptor T-cell therapy, a relatively new advancement in the world of immuno-oncology and thereby also discussing its advantages, side effects and future challenges.

摘要

尽管取得了重大进展,但复发和持续性恶性肿瘤仍是肿瘤学家面临的主要挑战。免疫疗法在诱导难治性恶性肿瘤持续缓解方面显示出显著潜力。嵌合抗原受体T细胞(CAR-T)疗法是一种经美国食品药品监督管理局(FDA)批准的较新的治疗方法。抗原受体与T细胞受体(TCR)细胞内信号域的嵌合配对使8号分化簇(CD8)细胞毒性T细胞能够靶向细胞表面标志物,而无需主要组织相容性复合体(MHC)激活。CAR广泛适用性及其潜在靶点不断扩大的另一个重要特征是,它们不仅能够与蛋白质结合,还能与碳水化合物和糖脂结构结合。它们的抗原特异性和靶向免疫反应在临床试验中显示出了有前景的结果,特别是在涉及B细胞恶性肿瘤和实体瘤的试验中。高缓解率和低复发率已在复发或难治性癌症的治疗中引起了范式转变。挑战包括细胞因子释放综合征等副作用、靶向非肿瘤毒性,以及在实体瘤治疗中复制其成功经验。副作用负担和高昂的治疗成本是可能阻碍其在全球范围内发展的主要障碍。尽管如此,正在进行的研究不仅会带来更大的治疗潜力,还会带来更有利于患者和成本的治疗方法。在本综述中,我们旨在为读者提供嵌合抗原受体T细胞疗法的概述,这是免疫肿瘤学领域中一项相对较新的进展,同时也讨论其优势、副作用和未来挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22b4/6314790/54f249ba5804/cureus-0010-00000003486-i01.jpg

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