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:Mutations in immunodeficiency-related genes may increase the risk of infection after CAR-T-cell therapy: a report of two cases.
对于 CAR-T 细胞治疗后出现持续性或复发性感染的患者,建议筛查免疫缺陷相关基因突变,其结果可能有助于 CAR-T 治疗后感染的管理。
背景:CAR-T 细胞疗法在B细胞恶性肿瘤中取得了前所未有的疗效。随着CAR-T细胞疗法应用日益增多,感染已成为CAR-T细胞输注后主要关注的问题之一。部分患者甚至出现难治性或复发性感染,给治疗、预防和监测策略带来挑战。然而,这些感染发生的机制尚不清楚。病例报告:本文报告两例CAR-T细胞治疗后感染病例。患者1为多发性骨髓瘤,接受抗B细胞成熟抗原(BCMA)CAR-T细胞治疗后,发生由白色念珠菌引起、持续超过5周的难治性尿路感染。全外显子组测序发现其携带IL-17RA基因突变。患者2患B细胞急性淋巴细胞白血病,接受抗CD19和抗CD22 CAR-T细胞联合治疗后,完全缓解维持超过4年;在这4年间,该患者发生5次肺炎。全外显子测序发现其携带CX3CR1基因突变。结论:对于CAR-T细胞治疗后出现持续性或复发性感染的患者,建议筛查免疫缺陷相关基因突变;筛查结果可能有助于CAR-T治疗后感染的管理。
BACKGROUND: Chimeric antigen receptor T-cell therapy (CAR-T) has yielded unprecedented efficacy in B-cell malignancies. With the increasing use of CAR-T-cell therapy, infection has become one of the major concerns after CAR-T-cell infusion. Some patients even develop refractory or recurrent infections, posing challenges in treatment, prophylactic, and monitoring strategies. However, the mechanisms underlying the development of these infections were not clear. CASE PRESENTATION: We report two cases of infection after CAR-T-cell therapy. Patient 1, diagnosed with multiple myeloma, received anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T (CAR-T)-cell therapy. He developed a refractory urinary infection lasting for over 5 weeks, which was caused by Candida albicans. Whole-exome sequencing revealed that he had an IL-17RA gene mutation. Patient 2, diagnosed with acute lymphoblastic B-cell leukaemia, received anti-CD19 and anti-CD22 CAR-T-cell cocktail therapy and remained in complete remission for over 4 years. The patient had pneumonia five times during the 4 years. Whole-exon sequencing revealed that he had a CX3CR1 gene mutation. CONCLUSION: For patients who develop persistent or recurrent infections after CAR-T-cell therapy, it is recommended to screen for immunodeficiency-related gene mutations, and the results may contribute to the management of infections post-CAR-T treatment.
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