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.
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- ORION CORP(FI)
- Filing Date
- 2021-12-14
- Publication Date
- 2026-06-22
AI Technical Summary
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.
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.
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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