UCLA researchers in the Department of Chemical and Biomolecular Engineering have developed chimeric antigen receptors that are responsive to human and mouse TGF-β (Transforming Growth Factor-Beta).
TGF-β is a pleiotropic cytokine found at high levels in a variety of pathogenic states, including solid tumors, fibrosis, and dysregulated wounds. Many anti-TGF-β antibodies exist, but few anti-TGF-β scFvs have been described.scFvs and antibodies share the ability to bind tightly and specifically to target proteins, in this case TGF-β.However, scFvs are superior due to the following features: the smaller size of scFv facilitates smaller packaging and lower production costs, scFvs allow for more flexibility when designing applications, and scFvs are easier to genetically engineer.
Researchers at UCLA have successfully described the sequences of scFvs that neutralize human and mouse TGF-β as well as chimeric antigen receptors (CARs) that robustly activate primary human T cells in response to TGF-β.
Therapeutics for diseases where high levels of TGF-β are present
The TGF-b CAR can be combined with tumor-targeting CARs or T cell receptors to render therapeutic T cells resistant to the immunosuppressive effects of TGF-b
Technical attributes of scFvs facilitate ease of production:
TGF-ß, Transforming growth factor-beta, chimeric antigen receptors, antibody, single-chain variable fragments, tumors, fibrosis, dysregulated wounds, therapy, immunotherapy, T-cell therapy, genetic engineering, gene therapy