CD229 CAR T cells (low-affinity variant)

CD229 CAR T cells (low-affinity variant) is an investigational cell-based immunotherapy designed for the treatment of multiple myeloma and other lymphoid malignancies. Developed by researchers at the University of Maryland School of Medicine, this therapy consists of chimeric antigen receptor (CAR) T cells targeting CD229 (also known as LY9), a cell surface receptor universally expressed on multiple myeloma plasma cells. To address the challenge of on-target off-tumor toxicity—specifically the killing of healthy T cells that express low levels of CD229—the CAR was engineered with a low-affinity binding domain derived from the 2D3 antibody via a single amino acid substitution. Additionally, these CAR T cells are engineered to overexpress the transcription factor c-Jun (CJUN), which enhances T cell expansion and persistence while reducing trogocytosis (antigen stripping). This dual-engineering approach aims to maintain potent anti-tumor efficacy while significantly improving the safety profile and durability of the therapy.

Other names

low-affinity CD229 CAR T cellsc-Jun overexpressing CD229 CAR T cells2D3 low-affinity variant CAR T cells