决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:The efficacy and safety of CD7 chimeric antigen receptor T-cell therapy for hematologic malignancies: a systematic review and meta-analysis.
我们的研究证实了CD7 CAR-T细胞的疗效和安全性,并为后续治疗提供了研究方向。
CD7CAR-T 细胞(CAR-T细胞)疗法是治疗血液系统恶性肿瘤的一种新兴方法,也是CAR-T细胞疗法的又一突破。
本研究总结了目前已经发表的关于CD7 CAR-T细胞的临床研究结果,并评估了CD7 CAR-T细胞疗法的安全性和有效性。
本研究纳入的13项研究中,共有200例患者接受了CD7 CAR-T细胞治疗,其中88例患者接受了自体CAR-T细胞治疗,112例患者接受了供者来源CAR-T细胞治疗。87%(80%-94%,I²=29.65%)的患者达到完全缓解。细胞因子释放综合征(CRS)的发生率为94%(88%-98%,I²=32.71%,p=0.12),而重度CRS(3级)的发生率为12%(5%-20%,I²=41.04%,p=0.06)。至于免疫效应细胞相关神经毒性综合征(ICANS)的发生率,为4%(1%-7%,I²=0,p=0.72)。通过对关键临床问题的分析,我们发现CAR-T细胞治疗后巩固性异基因造血干细胞移植(allo-HSCT)可显著提高生存率并避免复发。因此,我们认为应提倡CD7 CAR-T细胞治疗后进行巩固性allo-HSCT。而未接受基因编辑的CD7 CAR-T细胞治疗患者的总生存期显著长于接受基因编辑的CD7 CAR-T细胞治疗患者。这提示基因编辑的CD7 CAR-T细胞可能带来一些潜在风险,从而限制患者的长期生存。
INTRODUCTION: CD7 chimeric antigen receptor T-cell (CAR-T cell) therapy is an emerging method for treating hematological malignancies, and is another breakthrough in CAR-T cell therapy. METHODS: This study summarizes the currently published clinical research results on CD7 CAR-T cells and evaluates the safety and effectiveness of CD7 CAR-T cell therapy. RESULTS: Among the 13 studies included in this study, a total of 200 patients received CD7 CAR-T cell therapy, including 88 patients who received autologous CAR-T cells, 112 patients who received donor derived CAR-T cells. 87% (80% -94%, I 2 =29.65%) of patients achieved complete remission. The incidence of cytokine release syndrome (CRS) was 94% (88% -98%, I 2 =32.71%, p=0.12), while the incidence of severe CRS (grade 3) was 12% (5% -20%, I 2 =41.04%, p=0.06). As for the incidence of immune effector cell-associated neurotoxicity syndrome (ICANS), it is 4% (1% -7%, I 2 =0, p=0.72). Through analysis of the key clinical issues, we found that consolidation allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CAR-T cell therapy can significantly improve survival and avoid recurrence. Therefore, we believe that the consolidation allo-HSCT after CD7 CAR-T cell therapy should be advocated. And patients who received CD7 CAR-T cell therapy without gene editing had significantly longer overall survival than those who received CD7 CAR-T cell therapy with gene editing. This suggests that gene edited CD7 CAR-T cells may pose some potential risks that limit the long-term survival of patients. CONCLUSION: Our study confirms the efficacy and safety of CD7 CAR-T cells and provides research directions for the subsequent treatment. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=502896, identifier CRD42024502896.
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