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CAR-T 细胞治疗在儿童实体瘤中的应用

英文原题:CAR T-Cell Therapy in Children with Solid Tumors.

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CAR T-Cell Therapy in Children with Solid Tumors.

PubMed 2023/03/16(内容时间) J Clin Med Q1 · IF 3.3(JCR 2025)

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中文摘要

化疗、放疗和手术疗效有限,推动创新疗法发展。CAR-T 通过体外基因改造患者自身淋巴细胞,使其识别并杀伤特定肿瘤细胞且不受MHC限制,已在儿童急性淋巴细胞白血病和非霍奇金淋巴瘤中取得显著成功,可能改善治疗选择有限儿童的结局和生活质量,但实体瘤疗效仍在研究。本综述介绍CAR修饰T细胞概念及拟提升儿童实体瘤治疗安全性的新设计,总结近期研究,并讨论限制疗效的挑战:抗原逃逸、免疫抑制性微环境、归巢和浸润不足、靶向肿瘤外组织效应及一般毒性。

展开英文摘要原文

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.

论文信息

作者
Kulczycka M、Derlatka K、Tasior J、Lejman M、Zawitkowska J
第一作者单位
Student's Scientific Association, Department of Pediatric Hematology, Oncology and Transplantation, Medical University of Lublin, Gębali 6, 20-093 Lublin, Poland.Poland
通讯作者单位
Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin, Gębali 6, 20-093 Lublin, Poland.Poland
文献类型
综述
期刊
Journal of clinical medicine2023 Mar 16
原文标识
PubMed 36983330 · DOI 10.3390/jcm12062326