19 August 2025
Single-domain antibodies (sdAbs) appear to be excellent targeting molecules for Chimeric Antigen Receptor (CAR)-T cell therapies! This has also nicely been summed up by Guo and Xi (link in comments).
CAR-T cells are engineered T cells that express a Chimeric Antigen Receptor (CAR) on their surface. This CAR allows the T cell to recognize and bind to a specific antigen on cancer cells. Although CAR-T has been a breakthrough and has already made a tremendous impact in the clinic for blood cancers, there are still some hurdles to overcome for solid cancers.
In the first generations, the antigen-binding domain of the various CARs consisted of single-chain Fv fragments, which are fusion proteins of the variable domains of the heavy and the light chain of a conventional antibody. Nowadays, the CAR field is moving rapidly towards the use of a single-domain antibody for antigen binding.
Reasons for using sdAbs in CAR-T:
- Higher stability than scFv
- No VH/VL mispairing
- Less prone to aggregate; less T cell exhaustion
- No linker; less immunogenic
- Capable of binding broader range of epitopes
QVQ has partnered with Assistant Professor Maria Themeli from the Department of Hematology of the Amsterdam UMC to further explore the best application of sdAbs in CAR-T.
In the Health-Holland TKI project “CAVI-R”, the consortium we will create next generation of CAR technologies that are based on QVQ’s sdAbs, which aim for safer and long-lasting anti-tumor function.
As a fee-for-service CRO, QVQ has already generated several panels of sdAb for CAR-T approaches and would be happy to help you out with yours as well!
