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:Treatment strategies for relapse after CAR T-cell therapy in B cell lymphoma.
CART19细胞疗法已获美国食品药品监督管理局批准,用于初始治疗后12个月内复发或对一线治疗难治的患者。
抗CD19CAR-T(CART19)细胞疗法的临床试验已在复发/难治性B细胞恶性肿瘤患者中显示出较高的总缓解率。CART19细胞疗法已获美国食品药品监督管理局批准,用于初始治疗后12个月内复发或对一线治疗难治的患者。然而,CART19细胞疗法仍缺乏持久缓解,30%-60%的患者最终会在CART19输注后复发。总体而言,CART19细胞疗法后复发患者的预后较差,针对这一患者群体的各种治疗策略已被广泛研究。CART19治疗失败大致可根据淋巴瘤细胞呈现CD19阳性或CD19阴性来分类。如果淋巴瘤细胞上保留CD19表达,可考虑再次输注CART19细胞或使用免疫检查点抑制剂重新激活先前输注的CART19细胞。当患者出现CD19阴性复发时,使用CAR T细胞靶向不同抗原(如CD20或CD22)、研究性化疗或造血干细胞移植是潜在的治疗选择。然而,CART19细胞疗法后复发大B细胞淋巴瘤的挽救治疗尚未得到充分探索,且基于临床医生的逐例决策进行。在本综述中,我们将重点关注迄今为止报道的挽救治疗,并讨论CART19细胞疗法后复发/难治性大B细胞淋巴瘤的管理。
Clinical trials of anti-CD19 chimeric antigen receptor T (CART19) cell therapy have shown high overall response rates in patients with relapsed/refractory B-cell malignancies. CART19 cell therapy has been approved by the US Food and Drug Administration for patients who relapsed less than 12 months after initial therapy or who are refractory to first-line therapy. However, durable remission of CART19 cell therapy is still lacking, and 30%-60% of patients will eventually relapse after CART19 infusion. In general, the prognosis of patients who relapse after CART19 cell therapy is poor, and various strategies to treat this patient population have been investigated extensively. CART19 failures can be broadly categorized by the emergence of either CD19-positive or CD19-negative lymphoma cells. If CD19 expression is preserved on the lymphoma cells, a second infusion of CART19 cells or reactivation of previously infused CART19 cells with immune checkpoint inhibitors can be considered. When patients develop CD19-negative relapse, targeting different antigens (e.g., CD20 or CD22) with CAR T cells, investigational chemotherapies, or hematopoietic stem cell transplantation are potential treatment options. However, salvage therapies for relapsed large B-cell lymphoma after CART19 cell therapy have not been fully explored and are conducted based on clinicians' case-by-case decisions. In this review, we will focus on salvage therapies reported to date and discuss the management of relapsed/refractory large B-cell lymphomas after CART19 cell therapy.
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