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’ve developed a terrific working relationship with the team at Retrogenix and intend to utilize their microarray technology as a standard screen for future targets. Jim and Jo have become trusted collaborators and we appreciate their flexibility and willingness to work with us through some challenging issues. The quality and timeliness of the data and reports are first rate. We’ve come to rely on their results as a dependable means to confirm results from traditional crossreactivity studies and to identify additional potential unexpected interactions.
Amy Bourdeau, ‎Senior Preclinical Development Coordinator, Bluebird bio