J Clin Invest:BCMA特异性CAR T细胞治疗多发性骨髓瘤的临床活性

2021-05-10 MedSci原创 MedSci原创

嵌合抗原受体(CAR)T细胞是一种有前景的血液学恶性肿瘤治疗方法。B细胞成熟抗原(BCMA)是多发性骨髓瘤(MM)的一个理想靶标。近日,研究人员进行了一项I期临床研究,探究CART-BCMA输注联合或

嵌合抗原受体(CAR)T细胞是一种有前景的血液学恶性肿瘤治疗方法。B细胞成熟抗原(BCMA)是多发性骨髓瘤(MM)的一个理想靶标。近日,研究人员进行了一项I期临床研究,探究CART-BCMA输注联合或不联合淋巴消融化疗对复发MM患者复治的疗效,研究结果已发表于J Clin Invest。

研究纳入复发/难治性MM的受试者,进行了自体T细胞慢病毒转导,该T细胞含有CD3ζ和4-1BB信号域的全人类BCMA特异性CAR(CART-BCMA)。25名受试者在3个队列中接受以下治疗:1)仅1-5 x 108个CART-BCMA细胞;2)环磷酰胺(Cy)1.5 g/m2 + 1-5 x 107个CART-BCMA细胞;以及3)Cy 1.5 g/m2 + 1-5 x 108个CART-BCMA细胞。未预定BCMA表达水平要求。

 

所有受试者的CART-BCMA细胞都被制备和扩增。治疗毒性包括细胞因子释放综合征和神经毒性,分别有8名(32%)和3名(12%),级别为3-4级,且可逆转。一名受试者在治疗严重CRS和脑病后,于第24天死于念珠菌血症和进展性骨髓瘤。第1组的4/9例(44%)、第2组的1/5例(20%)和第3组的7/11例(64%)患者出现了缓解(基于治疗对象),包括5例部分缓解、5例非常好的部分缓解和2例完全缓解,其中3例在11、14和32个月时仍在继续。缓解者中残留的MM细胞上的BCMA表达减少;大多数人在病情进展时表达增加。缓解和CART-BCMA扩增与CD4:CD8 T细胞比例和白血病前产品中CD45RO-CD27+CD8+T细胞的频率有关。

综上所述,该研究结果表明,CART-BCMA输注联合或不联合淋巴消融化疗,可有效治疗复发的MM患者。

 

原始出处:

 

Adam D Cohen, et al., B cell maturation antigen-specific CAR T cells are clinically active in multiple myeloma. J Clin Invest. 2019 Mar 21;129(6):2210-2221. doi: 10.1172/JCI126397.

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    2022-02-08 jml2009
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    2021-05-12 yykkxiaodou
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    2021-05-10 ms3000001821055913

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