Specificity screening of CAR T cells

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 off-target activity that could promote an inappropriate immune response and be very dangerous for the patient.

As we have developed a methodology for labelling and screening whole CAR T cells, our technology is now widely used for assessing both the finalised engineered cells as well as the precursor antibody/scFv.

Retrogenix is now a standard part of non-clinical safety assessment for developers of novel CAR T cell therapies. Specificity screening data were included in the BLA submissions for Novartis’ Kymriah in the US and EU.

Screen scFvs or whole CAR T cells

Retrogenix has two approaches for off-target screening of CAR T cells:

  • 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 original antibody/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 screening capabilities then please get in touch and we can arrange a presentation for your team.

CAR T cell specificity screen for safety assessment of novel immunotherapies

Download our poster describing the how the Retrogenix human cell microarray technology has been optimised to screen whole CAR T cells for specific interactions, helping reduce the risk of unanticipated off-target adverse effects in the development of novel immunotherapies.

Download poster

FAQ: “How long does a screen take?”

Full projects typically take around 6-8 weeks from when we receive materials through to delivering the results and data package. Some high throughput lead selection projects are suitable for our ‘cut-down’ service which takes as little as 3 weeks. Longer lead times (for example 12 weeks) may be required for some studies including projects where a new detection method is being used as this will need to be optimised with the Retrogenix technology.

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Pfizer
The University of Sheffield
Aveo Oncology - The Human Response
Theraclone Sciences
BioInvent
AstraZeneca
Bluebird Bio
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The Center for Infectious Disease Research
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The University of Copenhagen
Lund University
MedImmune
NIH - National Institutes of Health
The University of Pennsylvania
Scripps Florida - The Scripps Research Institute
Peptinnovate Ltd - Unlocking Nature's Potential
We had a great interaction with the Retrogenix team. Their platform has helped us to identify 4 novel membrane-protein interactions that may prove pivotal to our future research aims.
Dr. Allan Lawrie, University of Sheffield, UK