CAR-NKT platform and 4-1BB engineering show promise against solid tumours in mouse models
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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, allowing off-the-shelf compatibility with lower graft-versus-host disease risk. In B16 melanoma and MC38 colon cancer models, the CAR-NKT cells outperformed CAR-T by infiltrating tumours and clearing M2 macrophages. The lecture also covers 4-1BB costimulation, which caused CAR-T death in up to 30% of some donors through TNFR-family signalling; mutating the TRAF-binding domain reduced that death and improved persistence. Dual-targeting CARs built with camelid single-domain VH antibodies performed best in dual-antigen models, are patented and licensed to a UK company. Still open: work on a soluble molecule that enhances CAR-T infiltration is under review at a GCI journal, and pancreatic cancer and glioblastoma orthotopic models are planned next.
Written by a model from the reports · updated 2 hours ago
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- youtube.comExpert 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.
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