Chimeric antigen receptor (CAR) T cell therapy involves engineering the patient’s own immune cells to recognise and attack a specific tumour. It has shown long-term promise in patients with advanced disease. As the therapy works by harnessing the immune system it is crucial that there is no CAR T cell cross reactivity, or off-target binding, that could promote an inappropriate immune response and be very dangerous for the patient.
As we have developed a methodology for labelling and analysing whole CAR T cells, our technology is now widely used for cross-reactivity screening of both the finalised engineered CAR T cells as well as the precursor antibody/scFv.
Retrogenix is now a standard IND-enabling safety assessment tool for developers of novel CAR T cell therapies. Our CAR T cell cross reactivity data were included in the BLA submissions for Novartis’ Kymriah in both the US and EU. Since this breakthrough approval in 2017, our screens continue to be widely used in CAR T cell therapy INDs / BLAs globally.
Screen scFvs or whole CAR T cells
Retrogenix has two approaches for CAR T cell cross-reactivity screening:
- Screen the antigen recognition element – the scFv
- Screen whole engineered CAR T cells
Early specificity screening helps select the right scFvs in order to maximise the chances of producing the most promising potential CAR T therapy. This can be followed later by screening of the whole engineered T cell (or the final scFv) to provide a more relevant assessment of off-target liability. As there may be a discordance between the off-target profile of the original antibody (or scFv) and the final engineered T cell it is possible to screen both to ensure that the binding has not been altered in development.
If you are interested in discussing our CAR T cell cross-reactivity screening capabilities then please get in touch and we can arrange a presentation for your team.