D0492 VHH CAR-T

D0492 VHH CAR-T is an investigational second-generation chimeric antigen receptor (CAR) T-cell therapy developed by Miltenyi Biotec and its subsidiary Lentigen Technology. The therapy is engineered to target the membrane-proximal region of mesothelin (MSLN), a cell-surface protein overexpressed in various solid tumors, including pancreatic and ovarian cancers. Unlike traditional CARs that use single-chain variable fragments (scFv), D0492 utilizes an alpaca-derived single-domain antibody (VHH or nanobody) for antigen recognition. This VHH-based approach is designed to maintain potency in the presence of soluble shed mesothelin, which can otherwise act as a decoy for traditional CAR-T therapies. The CAR construct incorporates a CD28 costimulatory domain and a CD3ζ signaling domain. Preclinical studies presented at AACR 2025 demonstrated significant anti-tumor activity and T-cell persistence in pancreatic cancer models.

Other names

anti-mesothelin VHH CAR-T