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实体瘤儿童的嵌合抗原受体T细胞疗法

CAR T-Cell Therapy in Children with Solid Tumors.

作者信息

Kulczycka Marika, Derlatka Kamila, Tasior Justyna, Lejman Monika, Zawitkowska Joanna

机构信息

Student's Scientific Association, Department of Pediatric Hematology, Oncology and Transplantation, Medical University of Lublin, Gębali 6, 20-093 Lublin, Poland.

Independent Laboratory of Genetic Diagnostics, Medical University of Lublin, Gębali 6, 20-093 Lublin, Poland.

出版信息

J Clin Med. 2023 Mar 16;12(6):2326. doi: 10.3390/jcm12062326.

Abstract

The limited efficacy of traditional cancer treatments, including chemotherapy, radiotherapy, and surgery, emphasize the significance of employing innovative methods. CAR (Chimeric Antigen Receptor) T-cell therapy remains the most revolutionizing treatment of pediatric hematological malignancies and solid tumors. Patient's own lymphocytes are modified ex-vivo using gene transfer techniques and programmed to recognize and destroy specific tumor cells regardless of MHC receptor, which probably makes CAR-T the most personalized therapy for the patient. With continued refinement and optimization, CAR-T cell therapy has the potential to significantly improve outcomes and quality of life for children with limited treatment options. It has shown remarkable success in treating hematological malignancies, such as acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL). However, its effectiveness in treating solid tumors is still being investigated and remains an area of active research. In this review we focus on solid tumors and explain the concept of CAR modified T cells, and discuss some novel CAR designs that are being considered to enhance the safety of CAR T-cell therapy in under-mentioned cancers. Furthermore, we summarize the most crucial recent reports concerning the solid tumors treatment in children. In the end we provide a short summary of many challenges that limit the therapeutic efficacy of CAR-T in solid tumors, such as antigen escape, immunosuppressive microenvironment, poor trafficking, and tumor infiltration, on-target off-tumor effects and general toxicity.

摘要

包括化疗、放疗和手术在内的传统癌症治疗方法疗效有限,这凸显了采用创新方法的重要性。嵌合抗原受体(CAR)T细胞疗法仍然是治疗小儿血液系统恶性肿瘤和实体瘤最具变革性的疗法。利用基因转移技术在体外对患者自身的淋巴细胞进行改造,并使其能够识别和摧毁特定的肿瘤细胞,而无需考虑MHC受体,这可能使CAR-T成为对患者而言最具个性化的疗法。随着不断完善和优化,CAR-T细胞疗法有可能显著改善治疗选择有限的儿童的治疗效果和生活质量。它在治疗血液系统恶性肿瘤,如急性淋巴细胞白血病(ALL)和非霍奇金淋巴瘤(NHL)方面已显示出显著成效。然而,其在治疗实体瘤方面的有效性仍在研究中,仍是一个活跃的研究领域。在本综述中,我们聚焦于实体瘤,解释CAR修饰T细胞的概念,并讨论一些正在考虑的新型CAR设计,以提高CAR-T细胞疗法在以下癌症中的安全性。此外,我们总结了有关儿童实体瘤治疗的最新关键报告。最后,我们简要概述了许多限制CAR-T在实体瘤中治疗效果的挑战,如抗原逃逸、免疫抑制微环境、归巢不良、肿瘤浸润、靶向脱瘤效应和全身毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/604b/10051963/26f9d9179d60/jcm-12-02326-g001.jpg

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