A TIGIT-based chimeric co-stimulatory switch receptor improves T-cell anti-tumor function.

ABSTRACT:

Background

Tumors can employ different mechanisms to evade immune surveillance and function. Overexpression of co-inhibitory ligands that bind to checkpoint molecules on the surface of T-cells can greatly impair the function of latter. TIGIT (T cell immunoreceptor with Ig and ITIM domains) is such a co-inhibitory receptor expressed by T and NK cells which, upon binding to its ligand (e.g., CD155), can diminish cytokine production and effector function. Additionally, the absence of positive co-stimulation at the tumor site can further dampen T-cell response.

Methods

As T-cell genetic engineering has become clinically-relevant in the recent years, we devised herein a strategy aimed at enhancing T-cell anti-tumor function by diverting T-cell coinhibitory signals into positive o

SUBMITTER: Hoogi S 

PROVIDER: S-EPMC6734436 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature