A Next-Generation Logic-Gated Switch-DARPin T-cell Engager with CD2 Co-Stimulation for Improved Safety & Efficacy in MSLN & EpCAM Co-Expressing Solid Cancer
- Clinical development of TCEs for solid tumours is often impaired by off-tumour ontarget and cytokine-release syndrome (CRS) triggered toxicities, and limited efficacy due to T-cell exhaustion
- We designed a logic-gated Switch-DARPin TCE (AND-gate) for tumour-localised immune activation targeting MSLN & EpCAM which are highly co-expressed in OC and other solid tumours. In addition, we built CD2 co-engagement into the Switch- DARPin inducing sustained T-cell proliferation and activity
- This approach provides an opportunity for novel cancer treatments through logicgated tumour-directed immune activation with increased efficacy & safety over single TAA-targeting modalities