scFv and CAR Cell Specificity Testing
Chimeric antigen receptor (CAR) T cell therapy involves engineering the patient’s own immune cells to recognize and attack a specific tumor. 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 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 analyzing whole CAR cells, our technology is now widely used for cross-reactivity specificity testing of both the finalized engineered CAR cells as well as the precursor antibody / scFv.
Retrogenix® Cell Microarray Technology is now a standard IND-enabling safety assessment tool for developers of novel CAR cell therapies. Our CAR cell specificity testing 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 cell therapy INDs / BLAs globally.
Cell Microarray Technology
Discover high quality, exploitable drug targets and mechanisms of action as well as screening for potential off-targets.
Off-Target Screening
Understand cross-reactivity to reduce toxicity-based attrition and aid lead selection.
Target Deconvolution
Accelerate phenotypic drug discovery through target deconvolution of phenotypic molecules.
Receptor Identification
Uncover receptors for proteins, viruses, and more complex ligands such as whole cells.
Screen scFv or Whole CAR Cells
Using the Retrogenix® Cell Microarray Technology, there are two approaches for CAR cell cross-reactivity screening:
- Screen the antigen recognition element – the scFv / antibody
- Screen whole engineered CAR cells
Early specificity testing helps select the right scFv in order to maximize the chances of producing the most promising potential CAR 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.
WEBINAR: Maximize Safer, Targeted Biologic Development with Smarter NAMs-Based Off-Target Screening
This webinar showcases how the Retrogenix® platform empowers smarter, earlier decisions across biologic formats. You’ll also learn how this platform, recently accepted into the FDA’s ISTAND Pilot Program, aligns with evolving regulatory support for NAMs and the shift toward reduced animal use.
Watch the Replay
Retrogenix® Data in Regulatory Applications
To help with understanding the role of Retrogenix® Cell Microarray Technology cross-reactivity screening in regulatory submissions, and to quantify the extent to which it is replacing methods such as IHC-based tissue cross reactivity (TCR) screening, we undertook a survey to find out how recently screened biotherapeutics are progressing. Pharma, biotech, and non-profit sponsors who have undertaken at least one project in the past two years were surveyed – click here to read more.
Frequently Asked Questions (FAQs) for CAR Cell Specificity Testing
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Can multi-specific or bi-specific cell therapies be profiled?
Yes. We can screen a range of multi-specific cell therapies, and we can even deconvolute which binding moiety is responsible for each interaction, providing the appropriate controls are available.
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Can other cell therapies be screened other than CAR cells?
The Retrogenix® platform is already optimized for a broad range of modalities and we are able to work with you to optimize the platform for additional cell therapies where required. Contact us to begin a conversation about your project.
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Should I profile the CAR cell or the precursor protein (eg scFv)?
We highly recommend sending both the scFv and CAR cell for specificity testing. Following some optimization steps, the High Peak team will work with you to decide whether to profile the scFv or CAR cell.