HPN328, a Trispecific T Cell-activating Protein Construct Targeting DLL3-Expressing Solid Tumors

Mary E. Molloy
Harpoon Therapeutics
April 27, 2024
Mol Cancer Ther
https://pubmed.ncbi.nlm.nih.gov/38670552

This article is currently being updated. View its version on PubMed.

https://pubmed.ncbi.nlm.nih.gov/38670552

Research summary

This study characterizes HPN328, a trispecific T cell–activating construct (TriTAC) designed to engage T cells via CD3, bind to DLL3 on tumor cells, and extend half-life through albumin binding. Preclinical evaluations demonstrated potent, dose-dependent cytotoxicity against DLL3-expressing small cell lung cancer (SCLC) cell lines, with concomitant T cell activation and cytokine release. In vivo studies using immunocompetent mice expressing human CD3ε showed significant tumor regression and long-term immunity upon tumor rechallenge.

Key outcome of the study

HPN328 effectively redirects T cells to kill DLL3-expressing tumor cells, demonstrating robust antitumor activity and inducing long-term immune memory in humanized CD3ε mouse models.

Model

Humanized CD3ε Knockin mouse model developed by genOway, enabling assessment of T cell engagers targeting human CD3 in an immunocompetent setting.

TARGET:
CD3E, DLL3
CD3 epsilon, Delta-like ligand 3

Keywords

Immuno-oncology, T cell engagers, Small cell lung cancer, DLL3 targeting, Trispecific antibodies

Technical specifications

Humanized Knockin, CD3ε, Immunocompetent mouse model, T cell engager evaluation

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