In a notable advancement in cell engineering research, scientists have developed the first ligand-based, piggyBac-transfected anti-EGFR CAR-T cells, targeting non-small cell lung cancer (NSCLC). NSCLC often overexpresses the Epidermal Growth Factor Receptor (EGFR), making it an ideal target for antitumor therapies.
Research Approach:
The study involved engineering chimeric antigen receptor (CAR)-T cells using the piggyBac transposon system.
Autologous artificial antigen-presenting cells and natural ligands of EGFR were utilized in the process.
The team tested three different ligands to identify the most effective CAR candidate.
Key Findings:
The unique engineering process created CAR-T cells that exhibited favorable level of CAR positivity and extremely high proportion of memory cells. These cells demonstrated potent antitumor activity against NSCLC both in laboratory (in vitro) and in animal models (in vivo). More importantly, their safety was demonstrated in both murine and non-human primate models, implying the readiness for clinical translation.
เงินทุน
This study was supported by the Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research (KAKENHI) nos. 20H03639 and 22K08996 and the Japan Agency for Medical Research and Development nos. 22ae0201006h0005, 22ama221312h0001, and 20ak0101048.
กระดาษต้นฉบับ
ชื่อบทความต้นฉบับ: Ligand-based, piggyBac-engineered CAR-T cells targeting EGFR are safe and effective against non-small cell lung cancers
วารสาร: Mol Ther Oncolytics
ดอย: 10.1016/j.omto.2023.100728