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:Case report: Dual-targeted BCMA and CS1 CAR-T-cell immunotherapy in recurrent and refractory extramedullary multiple myeloma.
在接受多轮化疗和放疗的复发难治性多发性骨髓瘤患者中,针对BCMA和CS1的双靶点CAR-T细胞疗法未能有效控制髓外复发。多发性骨髓瘤中MYBL2表达升高与较差的预后相关。
CAR-T细胞免疫疗法的发展显著提高了多发性骨髓瘤的治疗效果。目前,包括BCMA、CS1、CD38、FcRH5和GPRC5D在内的多种靶点正在研究中。尽管取得了这些重大进展,但抗原逃逸、CAR-T细胞持久性有限以及肿瘤微环境的复杂性等挑战仍然存在,导致治疗后复发。病例介绍:我们报告了一例复发难治性多发性骨髓瘤(RRMM)患者,在接受多轮放疗和化疗后,于下肢肌肉中出现了巨大的髓外浆细胞瘤。该患者接受了靶向BCMA和CS1的CAR-T细胞免疫治疗;然而,尽管接受了治疗,肿瘤仍出现进展。随后对髓外浆细胞瘤进行了手术切除。将肿瘤组织与邻近组织进行比较后,发现肿瘤组织中MYBL2表达增高,这可能导致了双靶点CAR-T细胞治疗后髓外复发未见改善。
BACKGROUND: The development of CAR-T-cell immunotherapy has notably elevated the efficacy of treating multiple myeloma. Currently, a variety of targets, including BCMA, CS1, CD38, FcRH5, and GPRC5D, are being investigated. Despite these significant advancements, challenges such as antigen escape, limited persistence of CAR-T cells, and the intricate nature of the tumor microenvironment persist, leading to relapses following treatment. CASE PRESENTATION: We report the case of a patient with recurrent and refractory multiple myeloma (RRMM) who developed a substantial extramedullary plasmacytoma in the muscles of the lower limb following multiple rounds of radiotherapy and chemotherapy. The patient underwent CAR-T-cell immunotherapy targeting BCMA and CS1; however, the tumor progressed despite treatment. Surgical resection of the extramedullary plasmacytoma was subsequently performed. Upon comparison of the tumor tissue with the adjacent tissue, increased expression of MYBL2 was noted in the tumor tissue, potentially contributing to the lack of improvement in extramedullary relapse after dual-targeted CAR-T cell therapy. CONCLUSIONS: In patients with recurrent and refractory multiple myeloma who underwent multiple cycles of chemotherapy and radiotherapy, dual-targeted CAR-T cell therapy aimed at BCMA and CS1 failed to effectively manage extramedullary relapse. Elevated expression of MYBL2 in multiple myeloma correlates with a poorer prognosis.
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