Expert lecture covers CAR-NKT platform and 4-1BB costimulation engineering for solid tumours
A 36-minute expert lecture on ImmuneZoom describes a mouse CAR-NKT platform in which NKT cells recognise lipid antigens in a CD1d-restricted manner, offer off-the-shelf compatibility with lower GVHD risk, and outperformed CAR-T in B16 melanoma and MC38 colon cancer models by infiltrating tumours and clearing M2 macrophages. 4-1BB costimulation caused CAR-T death up to 30% in some donors via TNFR-family signalling, and mutating the TRAF-binding domain reduced death and improved persistence. Dual-targeting CARs built with camelid single-domain VH antibodies worked best in dual-antigen models, are patented and licensed to a UK company, and work on a soluble molecule enhancing CAR-T infiltration is submitted to a GCI journal, with pancreatic cancer and GBM orthotopic models planned next.
Source: youtube.com