Chimeric antigen receptor (CAR) recognition is limited to membrane antigens, which represent around 10 % of the total proteins expressed, whereas TCRs (T cell receptor) have the advantage of targeting any peptide resulting from cellular protein degradation. However, CARs have an advantage over TCRs in requiring a much simpler intracellular signaling machinery. Scientists at Oslo University Hospital (Norway) have invented a novel receptor construct utilizing the target specificity of a TCR, with the more simple signaling machinery of a CAR. The construct is functional in both T cells and NK cells and open new therapeutic avenues by combining the killing efficiency of NK cells with the target recognition of TCRs and the simplicity of a CAR.
The main applications for the TCR-CAR is within therapeutic use: anti-cancer adoptive cell transfer (ACT). The construct may be transferred to effector cells (T cells or NK cells) by mRNA electroporation or viral transduction. The recognition of the target will depend on the peptide-MHC (pMHC) complex. Inven2 AS seeks to out-license the IP.
The scientists have cloned, expressed and killed target cells in a specific manner using two different constructs to redirect T cells and the NK cell line NK-92 (ATCC strain). As a proof of concept they have used DMF5 TCR-CAR (HLA-A2-MART1 specific TCR) and Radium-1 TCR-CAR (HLA-A2-TGFbRII frameshift specific TCR), however the invention can be used for converting other TCRs into TCR-CARs as well, followed by subsequent introduction into T cells or NK cells. For more information see Walseng et al., 2017 (Nature Scientific Reports).
PCT application filed March 5th 2018 (WO2019069125).
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