Development of Antigen-specific Chimeric Antigen Receptor KHYG-1 Cells for Glioblastoma

Abstract

Background/aim: Glioblastoma is the most common cancer among primary brain tumors, however, its prognosis and treatment advances are very poor. Here, we investigated whether c-Met, FOLR1, and AXL proteins are promising targets for chimeric antigen receptor (CAR) T-cell therapy, for they are known to be over-expressed in a variety of solid tumors.

Materials and methods: CAR constructs were prepared and CAR KHYG-1 cells targeting c-Met, FOLR1, or AXL were made by lentiviral transduction. The activity of CAR KHYG-1 cells against cancer cells was measured by cytokine secretion and cell lysis assays.

Results: c-Met and AXL were over-expressed in most glioblastoma cell lines (11/13), but not in neuroblastoma cell lines (0/8). FOLR1 was over-expressed only in one among 16 glioblastoma cell lines. Our antigen-specific CAR KHYG-1 cells eradicated target positive glioblastoma cells selectively.

Conclusion: Anti-c-Met and anti-AXL CAR NK or T cells could be effective in glioblastoma cells.

Keywords: AXL; Chimeric antigen receptor; FOLR1; KHYG-1; c-Met; glioblastoma; natural killer cell.