Zymeworks Presents Preclinical Data on Trispecific T Cell Engager Therapeutic Programs at the Society for Immunotherapy of Cancer (SITC) Conference

We are pleased to present preclinical data associated with our Trispecific T Cell Engager (TriTCE) therapeutic programs in two poster presentations at the annual SITC Conference, taking place November 1-4 in San Diego, CA.

The poster presentation titled “TriTCE Co-Stim: A novel trispecific T cell engager platform, with integrated CD28 costimulation, engineered to widen the therapeutic window for treatment of poorly infiltrated tumors” (Abstract #1372) shows the safety profile, anti-tumor properties, and the mechanism of action of how heterodimeric costimulatory trispecific TCE (TriTCE Co-stim) antibodies with silenced Fc gamma function to optimally engage CD3, CD28, and CLDN18.2.

Key Highlights:

  • Molecular format optimized with conditional CD28-costimulation in context of CD3 T-cell engager.
    • CD28 paratope in lead format exhibits no T-cell binding in absence of CD3 binding.
    • T-cell agonism and co-stimulation are tumor-target engagement dependent.
  • Lead CLDN18.2 TriTCE Co-Stim displays no systemic toxicity or peripheral cytokine release in murine toxicity model.
    • Mediates improved tumor regression with an increase of activated intratumoral T cells in vivo.
    • Exhibits equivalent tumor cell cytotoxicity and T-cell subset expansion in vitro to that achieved with combination of CD3 and CD28-engaging bispecific TCEs but with reduced cytokine release.
  • TriTCE Co-Stim has the potential to provide more durable responses, re-invigorate tumors with low T cell infiltration, and avoid potential toxicity liabilities, such as systemic cytokine release, key factors that may contribute to improved clinical outcomes.


In the poster presentation titled TriTCE CPI: a novel trispecific T cell engager platform with integrated PD-1/PD-L1 checkpoint inhibition engineered for the treatment of immunosuppressed tumors(Abstract #1396) shows TriTCE CPIs with integrated CD3 and PD-L1 engagement (via an engineered PD-1 domain) have the potential to enhance T cell responses in immunosuppressed and exhausted T cell microenvironments.

Key Highlights:

TriTCE CPIs have been formatted and designed to:

  • Overcome PD-L1 mediated tumor resistance mechanisms that can limit the efficacy of traditional bispecific TCEs.
  • Promote increased antitumor activity in PD-L1high tumors and with exhausted T cells and may improve responses in settings of primary resistance.
  • Promote increased antitumor activity in PD-L1low tumors and in tumors with inflammation-induced PD-L1 upregulation and may improve responses in settings of acquired resistance.
  • Avoid T cell activation in the absence of tumor cell engagement.


Additional information on our TriTCE therapeutic programs, can be found in the posters presented at the annual American Association for Cancer Research (AACR) Conference in April 2023.