Chimeric Antigen Receptor T-Cells (CAR-T) Technology

Chimeric Antigen Receptor (CAR)-T cell technology is based on gene therapy technology to modify T cells.

There are three key elements to this technology:

1.     A genetically modified T cell receptor based on B cell antibody gene and T cell receptor gene.

2.     A gene transfer tool that can effectively modify T cells.

3.     The modified T cells that boost the immune system and helps to maintain the good function inside the body.

CAR-T cell technology is a cancer targeting live drug in which the CAR directs the modified T cells to target and kill cancer. CAR-T can target a cancer cell by binding to specific cancer cell surface antigen. Many cancer cell surface antigens have been tested for CAR-T cell technology. The most important factor to the success of CAR-T cell technology is the efficiency of gene transfer into T cells. Most CAR-T cell technologies use lentivirus vector as gene transfer tool because lentivector can efficiently enter T cells and maintain a prolonged gene expression.

The most effective CAR-T design has been the CD19-specific CAR. The 3^rd generation CAR uses the T cell co-stimulatory factor 4-1BB signal to activate T cell, which can promote the proliferation of T cells and maintain a prolonged therapeutic effect. Although effective, 4-1BB-based CD19-CAR-T cell technology is known to cause severe reactions including neutropenia, cytokine release syndrome (CRS), tumor lysis syndrome, fever, hypotension, and sometime neuropathy. Which is in one had, a rapid and robust method to kill cancer cells, it can trigger a strong CRS that can be lethal. Many CD19-CAR-T cell treated leukemia patients require intensive care unit (ICU) after developing CRS.  

CAR-T Cell Therapy at GIMI

GIMI laboratory uses an advanced 4^th generation CAR design (4SCAR), which has a unique feature: low or no severe CRS. After years of clinical trials, CD19-specific 4SCAR-T has demonstrated cancer remission rate similar to the 3^rd generation CAR but no severe side effect!

Based on the 4^th generation CAR-T design, we have developed more than 100 CAR-T target schemes, which include the vast majority of cancer types.

In 2015, we reported a 3-year follow-up of the 4SCAR19 trial in the annual meeting of the American Society of Hematology (ASH). The phase I/II study included more than 200 patients with leukemia and more than 30 patients with stage III/IV advanced lymphomas. After 4SCAR19 treatment, the prognosis of these patients was significantly improved, and the response rate of acute lymphoblastic leukemia patients was up to 94%, and more than 80% achieved complete remission (CR). The 4SCAR technology is internationally advanced.