Chimeric TGF-beta signaling receptor (CTSR)

The Chimeric TGF-beta Signaling Receptor (CTSR) is a novel synthetic receptor platform designed to enhance the efficacy of Chimeric Antigen Receptor (CAR) T-cell therapies in solid tumors. Developed primarily by researchers at Children's Hospital Los Angeles (CHLA), the CTSR functions as a 'signal converter' that traps immunosuppressive TGF-beta within the tumor microenvironment and transforms it into a potent stimulatory signal for the T-cells. By fusing the extracellular binding domain of TGFBR2 with intracellular Toll-like receptor (TLR) signaling components like MyD88, the CTSR allows engineered T-cells to thrive and maintain cytotoxic function in hostile, TGF-beta-rich environments that typically exhaust conventional CAR-T products. This technology is currently being evaluated in Phase 1 clinical trials for pediatric solid tumors, including neuroblastoma and osteosarcoma, where it is often paired with CARs targeting the B7-H3 (CD276) antigen.

Other names

Chimeric TGFB signaling receptorTGF-beta switch receptorTGFBR2-MyD88 fusion receptorCTSR-armored CAR-T

The CTSR is a synthetic 'switch receptor' engineered into CAR T-cells to overcome the immunosuppressive effects of the tumor microenvironment. It consists of the extracellular domain of the TGF-beta receptor type II (TGFBR2) fused to the intracellular signaling domains of Toll-like receptor (TLR) adapters, specifically MyD88 and IRAK. When the receptor binds to immunosuppressive TGF-beta in the tumor, instead of inhibiting the T-cell, it triggers a stimulatory TLR-mimicking signal that enhances T-cell survival, proliferation, and anti-tumor activity.