Yu Cao, Managing Director of CADA Biosciences, shared on LinkedIn:
“1/1,000 of the conventional dose, META10-19 achieved a remarkable 92.3% ORR in DLBCL, reaffirming the dominance of metabolically enhanced CAR-T therapy.
7 months after Leman Biotech reported the striking efficacy of META10-19 in B-ALL, this autologous CD19 CAR-T therapy has raised the bar once again: In DLBCL, it demonstrated an exceptional combination of ultra-low dosing, high potency, and a favorable safety profile.
- META10-19 in B-ALL
- META10-19 in DLBCL
My notes:
- META10-19 can be manufactured from just ~100 mL of peripheral whole blood, avoiding the need for conventional leukapheresis. This simplified manufacturing process could make it accessible to patients who are too frail or otherwise unsuitable for leukapheresis.
- All patients exhibited robust in vivo expansion of META10-19, reaching a median peak of 660.7 CAR-T cells/μL, highlighting the therapy’s potent expansion kinetics and sustained persistence.
Why IL-10?
We have studied cytokines that enhance T-cell fitness for many years. While IL-10 is well known for modulating inflammatory responses through the JAK/STAT pathway, its role as a metabolic regulator has long been underappreciated. While a few recent studies suggested that IL-10 is one of the key regulators of T-cell metabolism, we had the opportunity to expand our knowledge of it’s impacts on OXPHOS and mitochondrial functions, which then lead to:
- Higher proliferation
- Less exhaustion
- More Tscm phenotype
(Nat Biotechnol. 2024 Nov;42(11):1693-1704.)
Hu Y, Zhang M, Gao M, et al. Ultralow-Dose Interleukin 10–Expressing Chimeric Antigen Receptor T Cells in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Nonrandomized Clinical Trial.”
Title: IL-10-expressing, anti-CD19 CAR T cells for patients with relapsed or refractory B-cell acute lymphoblastic leukaemia: an open-label, single-arm, phase 1 study
Authors: Qianwen Xu, Yugang Guo, Min Gao, Lei Xue, Hui Xu, Hui Li, Xuhan Zhang, Chongling Liu, Youjia Li, Qian Chen, Jingjing Ren, Karthik Sathiyanadan, Yongxian Hu, Li Tang, He Huang, Xingbing Wang
Read the Full Article.
Title: Ultralow-Dose Interleukin 10–Expressing Chimeric Antigen Receptor T Cells in Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Authors: Yongxian Hu, Mingming Zhang, Min Gao, Yetian Dong, Shan Fu, Yiling Li, Xunuo Zhu, Jingjing Feng, Ruimin Hong, Guoqing Wei, Duoduo Zhao, Jiazhen Cui, Simao Huang, Tinging Yang, Daojun Bai, Baoyun Cheng, Yuanbin Cui, Jingjing Ren, Chongling Liu, Youjia Li, Qian Chen, Zhan Zhou, Dongrui Wang, Yugang Guo, Li Tang, Xingbing Wang, He Huang
Read the Full Article.
