ProTIA (T-Cell Engagers)

Protease Triggered Immune Activator

Unique class of bispecific T-cell activators with long half-life and superior safety compared to other bispecific formats.


XTEN technology has been applied to develop a unique class of bispecific T cell activators with long half-life and superior safety compared to other bispecific formats. ProTIA molecules combine three mechanisms to widen their therapeutic window: 1) The bulky size of XTEN reduces extravasation in healthy tissue compared to the leaky vasculature in tumors; 2) ProTIA molecules do not bind healthy cells which show no or limited expression of tumor antigens; 3) ProTIA molecules are preferentially activated in the tumor environment by tumor-associated proteases.

XTENylation prevents T cell activation by ProTIA therapeutics until the molecule reaches tumor tissue and XTEN is released by tumor-associated proteases. ProTIA molecules are designed to be activated by proteases with known overexpression in the tumor environment. XTENylation effectively blocks synapse formation between T cells and tumor cells. Once the XTEN polymer has been released from ProTIA by one of multiple tumor-associated proteases, the activated bi-specific T cell/tumor cell binder exhibits IC50 values in the low picomolar range.

ProTIA molecules are efficiently produced by microbial fermentation. The hydrophilic nature of XTEN facilitates proper folding of the tumor- and T cell binding domains and minimizes the formation of multimers and aggregates.