嵌合抗原受体-T细胞治疗儿童肿瘤的临床研究进展

发布时间：2018-08-15 11:29

【摘要】：儿童肿瘤患者的5年生存率已达80%以上,但仍有部分复发难治性肿瘤通过传统治疗手段难以取得理想疗效。嵌合抗原受体(CAR)-T细胞技术的发展为治愈这些肿瘤带来了希望。CAR-T细胞通过非MHC限制性的方式识别肿瘤相关抗原,抗肿瘤能力显著增强,目前已发展到第四代。靶向CD19的CAR-T细胞治疗复发难治性急性淋巴细胞白血病缓解率高达90%,且可以通过桥接造血干细胞移植、供者CAR-T细胞输注等手段辅助白血病的治疗。实体瘤方面,靶向GD2的CAR-T细胞治疗神经母细胞瘤具有良好的反应性,但对其他实体瘤效果欠佳。CAR-T细胞治疗可能出现细胞因子释放综合征、脱靶效应、肿瘤溶解综合征、插入突变等毒副反应。靶向CD19的CAR-T细胞治疗虽有很高的缓解率,但复发率较高,包括CD19~+和CD19~-复发,其机制尚需进一步研究。
[Abstract]:The 5-year survival rate of children with tumor was over 80%, but there were still some relapsed and refractory tumors which were difficult to obtain ideal curative effect by traditional treatment. With the development of chimeric antigen receptor (CAR)-T cell technology, it is hoped that CAR-T cells can recognize tumor-associated antigens in a non-MHC restrictive way, and the anti-tumor ability has been significantly enhanced. At present, CAR-T cells have been developed to the fourth generation. The remission rate of CD19 targeted CAR-T cells in the treatment of relapsed refractory acute lymphoblastic leukemia is as high as 90%, and can be assisted by bridging hematopoietic stem cell transplantation and donor CAR-T cell infusion. In solid tumors, CAR-T cells targeting GD2 have good response to neuroblastoma, but the effect of CAR-T cell therapy on other solid tumors may appear cytokine release syndrome, miss effect and tumor lysis syndrome. Insert mutation and other toxic side effects. Although CAR-T cell therapy targeting CD19 has a high remission rate, the recurrence rate is high, including CD19 ~ and CD19 ~-recurrence, the mechanism of which needs to be further studied.
【作者单位】：浙江大学医学院附属儿童医院血液肿瘤科;
【基金】：浙江省自然科学基金(LY15H080004)
【分类号】：R730.51

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