Transforming Growth Factor-Beta (TGF-β)-Responsive Single-Chain Variable Fragments And Chimeric Antigen Receptors

Summary

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).

Background

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.

Innovation

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.

Applications

Therapeutics for diseases where high levels of TGF-β are present

Advantages

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:

• Apply less stress to gene delivery modalities
• Can be collected directly from media in which it was produced
• More easily used in genetic engineering and gene therapy applications

Patent Status

Additional Patents Pending

Related Materials

• Chang, ZeNan L., Pamela A. Silver, and Yvonne Y. Chen. "Identification and selective expansion of functionally superior T cells expressing chimeric antigen receptors." Journal of translational medicine 13.1 (2015)