Nicola Ferrari Highlights Study on Allogeneic CD19 CAR-T Cells for Refractory Lupus Nephritis
Nicola Ferrari, Director of Translational Science Lead for Respiratory and Immunology at AstraZeneca, shared a post on LinkedIn about a paper by Xiaobing Wang et al. published on Nature:
“Allogeneic CD19-targeting T cells for treatment-refractory systemic lupus erythematosus: a phase 1 trial
In a small trial of patients with lupus nephritis, treatment with allogeneic T cells with a CD19 chimeric antigen receptor inserted into the T cell receptor locus and deletion of the PD-1 (PDCD1) gene were safe and associated with reduced disease activity.
– Commercial autologous anti-CD19 chimeric antigen receptor-T cell therapies are effective in B cell malignancies and autoimmune diseases but are limited by personalized manufacturing, high costs and the risk from random chimeric antigen receptor insertion into the genome.
– To overcome these challenges the authors developed YTS109, a hypoimmune allogeneic T cell product engineered using CRISPR–Cas9 to knock out TRAC, PD1, HLA-A, HLA-B and CIITA, with a CD19-targeting synthetic TCR and antigen receptor (STAR) integrated into the TRAC locus to enable physiological, TCR-like signaling.
– In this study, the authors reported the first application of YTS109, in patients with refractory SLE complicated by severe LN. Four of five patients showed a rapid and sustained reduction in SLE disease activity score (mean 31.30–5.35 by M6), while 1 patient showed a mild refractory flare-up at M6.
– B cell depletion was achieved in all patients, and renal B cell depletion confirmed in two patients who underwent repeat kidney biopsies, coinciding with marked clinical remission in these individuals.
– These results demonstrate that YTS109 induced immune resetting and clinical remission, including renal structural restoration, potentially offering a promising therapy for refractory SLE with severe lupus nephritis
– This study has several limitations, including its single-arm design, small sample size (n = 5) and short follow-up. Larger, longer-term studies are needed to confirm the durability and generalizability of responses.”
Title: Allogeneic CD19-targeting T cells for treatment-refractory systemic lupus erythematosus: a phase 1 trial
Authors: Xiaobing Wang, Yi Zhang, Huimin Wang, Xin Wu, Chao He, Suxian Lin, Kun Pang, Yang Li, Yue Chen, Xiaojing Tang, Xin Liu, Jiazheng Wang, Songying Ye, Ran Yan, Tongxiang Guan, Bing Dai, Jing Lu, Haiyan He, Li Lin, Hongjuan Lu, Ting Li, Ling Zhou, Lingying Ye, Juan Zhao, Yanfang Liu, Na Ta, Jun Wu, Wanshi Cai, Zhe Wan, Shasha Zhang, Ruya Sun, Xueqiang Zhao, Jiasheng Wang, Yong Lin, Beifang Ning, Zhengqing Zhao, Xiaofeng Tang, Juan Du, Zhiguo Mao, Yanran He, Hongli Zheng, Lingyun Sun, Xin Lin and Huji Xu
Read the full article.
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