Titering of Chimeric Antigen Receptors on CAR T Cells enabled by a Microfluidic-based Dosage-Controlled Intracellular mRNA Delivery Platform.
Yu-Hsi ChenRuoyu JiangAbraham Phillip LeePublished in: bioRxiv : the preprint server for biology (2023)
Chimeric antigen receptor (CAR) T-cell therapy shows unprecedented efficacy for cancer treatment, particularly in treating patients with various blood cancers, most notably B-cell acute lymphoblastic leukemia (B-ALL). In recent years, CAR T-cell therapies are being investigated for treating other hematologic malignancies and solid tumors. Despite the remarkable success of CAR T-cell therapy, it has unexpected side effects that are potentially life threatening. Here, we demonstrate the delivery of approximately the same amount of CAR gene coding mRNA into each T cell propose an acoustic-electric microfluidic platform to manipulate cell membranes and achieve dosage control via uniform mixing, which delivers approximately the same amount of CAR genes into each T cell. We also show that CAR expression density can be titered on the surface of primary T cells under various input power conditions using the microfluidic platform.
Keyphrases
- cell therapy
- high throughput
- stem cells
- acute lymphoblastic leukemia
- single cell
- mesenchymal stem cells
- circulating tumor cells
- genome wide
- binding protein
- poor prognosis
- mass spectrometry
- copy number
- label free
- gene expression
- long non coding rna
- dna methylation
- high resolution
- young adults
- allogeneic hematopoietic stem cell transplantation
- single molecule
- genome wide analysis