Enhancement of CAR T cell function by modification of chimeric antigen receptor (CAR) spacers

By integrating Ig-like C1 domains from SIRP-alpha and multimerization domains into CARs, off-target binding issues are mitigated, ensuring efficient and tolerable cytotoxicity in CAR T-cell therapy.

JP7877319B2Active Publication Date: 2026-06-22ORION CORP(FI)
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Patent Information

Application Number
JP2023536337
Authority / Receiving Office
JP · JP
Patent Type
Patents
Current Assignee / Owner
Priority Date
2020-12-16
Filing Date
2021-12-14
Publication Date
2026-06-22
Estimated Expiration
2041-12-14

AI Technical Summary

Technical Problem

Current chimeric antigen receptors (CARs) in CAR T-cell therapy face issues with off-target binding to Fc receptor-expressing cells, leading to unwanted side effects such as myeloid activation, inflammation, and decreased CAR T cell activity, which need to be refined to achieve efficient and tolerable cytotoxicity.

Method used

Incorporating an extracellular spacer in CARs composed of Ig-like C1 domains from signal regulatory protein alpha (SIRP-alpha) and multimerization domains, such as IgG hinge regions and CD28 extracellular domains, to prevent interaction with Fc receptors, thereby reducing off-target binding and enhancing CAR T cell function.

Benefits of technology

The modified CARs effectively minimize off-target interactions, maintaining CAR T cell activity and efficacy by avoiding activation-induced cell death and sequestration, thus improving therapeutic outcomes.

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Abstract

The present invention relates to chimeric antigen receptors (CARs) containing an inert and modifiable spacer that avoids off-target binding by Fc receptor (FcR)-expressing cells in CAR T cell therapy. The spacer is based on the Ig-like C1 domain of signal-regulatory protein alpha.
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Citation Information

Patent Citations

  • Immunomodulatory fusion proteins and uses thereof

    JP2018508219A

  • Specific Chimeric Antigen Receptor T Cells Targeting to CD47, Preparation Method and Application Thereof

    US20190209671A1