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Abstract: FR-PO0841

Establishment of a Rapid and Automatic Eli-TR Chimeric Antigen Receptor T Cell Manufacturing and Release Platform for the Treatment of Autoimmune Diseases, Including Membranous Nephropathy (MN)

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Yang, Yong, Fosunkairos (Shanghai) biotechnologies Ltd., Shanghai, China
  • Shan, Aidong, Fosunkairos (Shanghai) biotechnologies Ltd., Shanghai, China
  • Xin, He, Fosunkairos (Shanghai) biotechnologies Ltd., Shanghai, China
  • Zhang, Jian, Fosunkairos (Shanghai) biotechnologies Ltd., Shanghai, China
  • Hou, Li, Fosunkairos (Shanghai) biotechnologies Ltd., Shanghai, China
  • Pingfan, Ma, Fosunkairos (Shanghai) biotechnologies Ltd., Shanghai, China
  • Dong, Yang, Fosunkairos (Shanghai) biotechnologies Ltd., Shanghai, China
  • Liu, Dan, Fosunkairos (Shanghai) biotechnologies Ltd., Shanghai, China
  • Lin, Chen Xi, Fosunkairos (Shanghai) biotechnologies Ltd., Shanghai, China
  • Liu, Qin, Fosunkairos (Shanghai) biotechnologies Ltd., Shanghai, China
  • Wang, Lishen, Fosunkairos (Shanghai) biotechnologies Ltd., Shanghai, China
  • Lei Zhang, Lei Zhang, Fosunkairos (Shanghai) biotechnologies Ltd., Shanghai, China
  • Zhang, Xianyan, Fosunkairos (Shanghai) biotechnologies Ltd., Shanghai, China
  • Zhao, Xiaojiao, Fosunkairos (Shanghai) biotechnologies Ltd., Shanghai, China
  • Wang, Chris, Fosunkairos (Shanghai) biotechnologies Ltd., Shanghai, China
  • Wang, Wenshi, Fosunkairos (Shanghai) biotechnologies Ltd., Shanghai, China
Background

Chimeric antigen receptor (CAR) T cell therapies have achieved notable success in treating B cell malignancies and recently have been repurposed to treat pathogenic B cells driven autoimmune diseases. To address the exhaustion issue caused by conventional manufacturing process, we established a rapid and automatic Eli-TR CAR-T platform based on a systematic investigation to balance desired young immune phenotype, potency and unmet need of cell numbers.

Methods

The Eli-TR CAR-T manufacturing production process includes peripheral blood mononuclear cells (PBMC) purification, T cells enrichment and activation followed by lentiviral transduction. 48, 72 and 96 hours of production time had been thoroughly investigated to optimize the CAR-T characters, function and the release QC testing. FKC289, an autologous dual anti-BCMA and anti-CD19 CAR-T product were manufactured and released using Eli-TR platformwithin 72 hours, and the phase I dose escalation IIT study was initiated to explore the safety and efficacy of FKC289 in patients with MN.

Results

For Eli-TR CAR-T platform setup, fit for purpose principle is the best approach for choosing the best manufacturing time.
FKC289 cells display a stem-like immune phenotype as indicated by not only more abundant naïve and stem central memory T cells also less exhausted T cells correlated to persist longer and promising deep clinical response. The transduction efficiency continued to increase until it reached the plateau suggests that a post-thawed culture interval may be a good option for releasing tests such as transduction efficiency and VCN per CAR+ cells. We have observed clinical safety and efficacy and persistency of our FKC289 in treating MN.

Conclusion

FKC289 cells manufactured on Eli-TR CAR-T platform had balanced the young phenotypic profile and sufficient cell quantities, and the best time for QC releasing tests.
Our early clinical observation indicates that FKC289 is safe and efficacious in treating patient with MN through deeper B cell depletion and reset of immune system because of its potency, persistency and low manufacturing cost.

Funding

  • Commercial Support – FosunKairos (Shanghai) biotechnologies Ltd., Shanghai, China

Digital Object Identifier (DOI)