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:Targeting GPRC5D in multiple myeloma.
我们提出了关于各类基于 GPRC5D 的疗法在 MM 治疗格局中潜在应用的见解,无论是单独使用还是与已有疗法联合。
引言:多发性骨髓瘤(MM)预后持续改善。免疫调节药物(IMiD)、蛋白酶体抑制剂(PI)和抗CD38单克隆抗体等疗法近期进展显著改善了患者结局。尽管如此,复发仍常见,患者可能对常规治疗产生耐药。嵌合抗原受体(CAR)T细胞疗法和靶向B细胞成熟抗原(BCMA)的双特异性抗体(BsAb)等新型疗法,为治疗选择有限的患者带来了优异结局。G蛋白偶联受体C组5成员D(GPRC5D)被认为是极具前景的靶点,临床试验早期结果显示其治疗复发或难治性多发性骨髓瘤应答率较高。 综述范围:本文综述靶向GPRC5D的CAR-T和BsAb治疗MM的疗效与安全性,重点介绍首个获FDA批准的靶向GPRC5D BsAb talquetamab。Talquetamab显示出有希望的应答率,并具有独特副作用特征。本文还讨论正在开展的talquetamab联合daratumumab、teclistamab等药物的临床试验。 专家意见:我们探讨基于GPRC5D的不同疗法单独或联合既有疗法在MM治疗方案中的潜在应用。
INTRODUCTION: The prognosis of multiple myeloma (MM) continues to improve. Recent progress in therapies, using immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and anti-CD38 monoclonal antibodies, has greatly improved patients' outcomes. Despite these advancements, relapses still happen often, and patients can become resistant to the usual treatments. Newer treatments, such as chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies (BsAbs) targeting B-cell maturation antigen (BCMA), have resulted in excellent outcomes in patients with limited treatment options. G protein - coupled receptor, class C group 5 member D (GPRC5D) is considered a very promising target with early results from clinical trials showing high response rates in patients with relapsed or refractory multiple myeloma. AREAS COVERED: This review covers the efficacy and safety of CAR-T and BsAbs targeting GPRC5D in MM, focusing on talquetamab - the inaugural FDA-approved BsAb targeting GPRC5D. Talquetamab has exhibited promising response rates alongside a distinctive side effect profile. Additionally, ongoing trials examining talquetamab in combination with agents like daratumumab and teclistamab are discussed. EXPERT OPINION: We offer insights into the potential utilization of various GPRC5D-based therapies in the treatment paradigm for MM, either independently or in combination with established therapies.
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