TGI-17a

TGI-17a is a preclinical-stage PD-1/IL-2 α-bias bispecific antibody fusion protein developed for the treatment of various cancers, including those resistant to standard immune checkpoint inhibitors. It is designed to selectively activate antigen-specific CD8+ T cells by combining PD-1 blockade with a biased IL-2 signal. The molecule features an IL-2 variant with an enhanced affinity for the IL-2 receptor alpha subunit (IL-2Rα/CD25) and significantly reduced affinity for the IL-2Rβγ signaling complex. This design promotes cis-activation, where the IL-2 signal is preferentially delivered to PD-1-expressing T cells within the tumor microenvironment, thereby maximizing anti-tumor efficacy while minimizing systemic toxicities like vascular leak syndrome typically associated with broad IL-2Rβγ activation. Preclinical studies have demonstrated superior anti-tumor activity compared to pembrolizumab and other bispecific constructs in syngeneic mouse models.