Zymeworks Presents New Data from Multiple Preclinical Development Programs at 2024

TriTCE Co-Stim: A next generation trispecific T cell engager platform with integrated CD28 costimulation, engineered to improve responses in the treatment of solid tumors 

Abstract: 6719

Session Category: Immunology

Session Title: Targeted ICEs

Low T cell infiltration and T cell anergy are challenges associated with the treatment of solid tumors with conventional CD3-engaging bispecific T cell engagers (TCEs)1. By optimizing “Signal 1” (CD3) and “Signal 2” (CD28) within the context of a single molecule, co-stimulatory trispecific TCEs (TriTCE Co-Stim) have the potential to increase therapeutic responses beyond that achievable by conventional CD3-based TCEs by stimulating T cell proliferation in patients with poorly infiltrated tumors and providing more durable anti-tumor control by enhancing T cell activation.

Key Results:

Relative to comparator bispecific TCEs, the lead CLDN18.2 TriTCE Co-Stim molecule mediates enhanced T cell-mediated killing of tumor cells at low E:T ratios, exhibits sustained T cell mediated activity in serial challenge assays and supports superior antitumor activity in humanized models of gastric cancer.

TriTCE Co-stim design facilitates obligate cis T cell binding and activation of CD28 that requires co-engagement of CD3 with no detectable cytokine levels observed upon incubation with human peripheral blood mononuclear cells in the absence of tumor target engagement.

CLDN18.2 TriTCE Co-stim was well tolerated in non-human primates upon repeat dosing, with minimal peripheral cytokine elevations and no on-target histopathological changes observed.

DLL3 TriTCE Co-Stim: A next generation trispecific T cell engager with integrated CD28 costimulation for the treatment of DLL3-expressing cancers

Abstract: 6716

Session Category: Immunology

Session Title: Targeted ICEs