Within immunotherapies, CAR-T cell therapies are an advancing technology that has gained recognition over the past decade.
The approved CAR-T cell therapy currently on the market are all 1) targeting cancer of liquid tissues and 2) based on autologous cells (i.e. the cells are obtained from the patients).
Despite the active research field, a breakthrough for solid cancer still has to be found.
The proprietary novel approach of CAR-T-uning, as developed in our given PoC project, is based on gene editing of a T cell inhibitor established by the Prof. Baier team, NR2F6, which results in a potent trigger of CAR-T therapy benefits.
NR2F6 is a distantly related member of the nuclear receptor family with a long history of successful drug discovery.
Milieu signals in the tumor immune microenvironment (TIME) cause a highly localised NR2F6 upregulation in resident tumour T cells. This is because NR2F6 has an inhibitory effect on T cells' activity that fosters tumor immune escape within the TIME.
Our approach involves CAR-T therapy using a CRISPR(Cas9) sgRNA/RNP transfection method that depletes NR2F6, thereby sensitising the CAR-T cells to improve their anti-tumor activity and response rate to therapy.
Mechanistically, NR2F6-modified CAR-T cells are more effective at killing cancer cells bearing the CAR-targeted antigen.
Taken together, NR2F6 is an intrinsic T lymphocyte factor that acts as an inducible intracellular cancer immune checkpoint and drives primary and acquired resistance to immunotherapy in solid tumors, leading to tumor progression.
Therefore, NR2F6-modified CAR-T plug-in technology appears as a unique therapy option for solid tumors.
