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:Multiple CAR-T cell therapy for acute B-cell lymphoblastic leukemia after hematopoietic stem cell transplantation: A case report.
常规化疗和造血干细胞移植(HSCT)后治愈率已达90%,但复发难治性(R/R)白血病患者经常规治疗后预后仍然较差。
B细胞急性淋巴细胞白血病(B-ALL)是儿童最常见的恶性肿瘤。经过常规化疗和造血干细胞移植(HSCT)后,治愈率已达90%,但复发难治(R/R)白血病患者经常规治疗后预后仍然较差。自FDA批准CD19 CAR-T细胞(Kymriah)用于治疗R/R B-ALL以来,针对R/R ALL的CAR-T细胞研究日益增多。本文报道一例ALL患者,异基因HSCT后复发,对鼠源scFv CD19 CAR-T获得完全缓解(CR),但15个月后复发。经人源化CD19 CAR-T治疗后获得部分缓解,患者最终经序贯CD22 CAR-T治疗后获得无病生存。通过比较同一患者不同CAR-T细胞的治疗结果,本病例提示多种CAR-T疗法对同一患者的髓内和髓外复发均有效且安全,CAR-T细胞的扩增和炎性细胞因子的释放与其疗效呈正相关。然而,仍需进一步开展大样本临床研究以进一步阐明。
B-cell acute lymphoblastic leukemia (B-ALL) is the most common childhood malignancy. The cure rate has reached 90% after conventional chemotherapy and hematopoietic stem cell transplantation (HSCT), but the prognosis of patients with relapsed and refractory (R/R) leukemia is still poor after conventional treatment. Since FDA approved CD19 CAR-T cell (Kymriah) for the treatment of R/R B-ALL, increasing studies have been conducted on CAR-T cells for R/R ALL. Herein, we report the treatment of a patient with ALL who relapsed after allogeneic HSCT, had a complete remission (CR) to murine scFv CD19 CAR-T but relapsed 15 months later. Partial response was achieved after humanized CD19 CAR-T treatment, and the patient finally achieved disease-free survival after sequential CD22 CAR-T treatment. By comparing the treatment results of different CAR-T cells in the same patient, this case suggests that multiple CAR-T therapies are effective and safe in intramedullary and extramedullary recurrence in the same patient, and the expansion of CAR-T cells and the release of inflammatory cytokines are positively correlated with their efficacy. However, further clinical studies with large sample sizes are still needed for further clarification.
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