Single cell RNA sequencing of TSCM predominnant allogeneic anti-BCMA CAR-T cells

We characterize the phenotype and heterogeneity of P-BCMA-ALLO1, a TSCM-predominant allogeneic CAR-T therapy targeting BCMA in heavily pretreated relapsed/refractory multiple myeloma. Our analyses showed that P-BCMA-ALLO1 has a high frequency of memory CD8+ T cells, and their abundance correlates with antitumor potency. This finding matches our other observations that memory phenotype and functionality correlates with antitumor efficacy, along with viability and cytotoxicity. Overall design: 18 different lots of research-grade P-BCMA-ALLO1 from 15 different healthy donors were run for scRNAseq to find correlates of antitumor potency

本研究对P-BCMA-ALLO1的表型与异质性进行了系统表征。P-BCMA-ALLO1是一种以干细胞记忆T细胞（TSCM）为主、靶向B细胞成熟抗原（BCMA）的同种异体嵌合抗原受体T细胞（CAR-T）疗法，适用于经多线治疗的复发/难治性多发性骨髓瘤患者。

分析结果显示，P-BCMA-ALLO1制剂中记忆性CD8+ T细胞占比颇高，其细胞丰度与抗肿瘤效能呈显著正相关。这一发现与我们此前的其他观测结果一致：记忆细胞表型、功能活性与抗肿瘤疗效、细胞存活能力及细胞毒性均具有相关性。

实验整体设计：本研究对来自15名健康供体的18批研究级P-BCMA-ALLO1制剂开展了单细胞RNA测序（scRNAseq），以挖掘与抗肿瘤效能相关的潜在标志物。