Zymeworks Presents New Data from Multiple Preclinical Development Programs at 2024

A readily implementable method for the rapid generation of cancer cell line spheroids was established and applied to over 50 distinct immortalized cancer cell lines derived from more than 10 tissue types, demonstrating varying morphological features with a success rate of >95%.

In vitro assays were developed to evaluate the spheroid penetration capability and 3D cytotoxic activity of multispecific antibodies and ADCs, enabling the interrogation of various antibody formats and payload classes.

These 3D models and assays serve as valuable functional tools that provide improved translation between in vitro and in vivo activity, supporting the characterization of therapeutic ADC candidates and their pipeline advancement.

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.

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