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

Molloy ME
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 evaluates the preclinical efficacy and safety of HPN328, a trispecific T cell–activating protein construct designed to target Delta-like ligand 3 (DLL3) on solid tumors. HPN328 aims to redirect T cells to DLL3-expressing cancer cells, promoting targeted tumor cell lysis.

Key outcome of the study

HPN328 demonstrated potent and specific cytotoxicity against DLL3-expressing tumor cells in vitro and led to significant tumor regression in vivo without notable off-target effects. These results support the potential of HPN328 as a therapeutic agent for DLL3-positive malignancies.

Mouse model

The study utilized a humanized mouse model developed in collaboration with genOway. This model expresses human DLL3 and features a reconstituted human immune system, allowing for the assessment of HPN328's activity in an in vivo setting that closely mimics human tumor-immune interactions.

TARGET:
Dll3
Delta-like 3, Delta3

Keywords

Oncology, Solid tumors, Immunotherapy, T cell engagement, Targeted therapy

Technical specifications

Humanized mouse model, Human DLL3 expression, Reconstituted human immune system, In vivo efficacy assessment, Tumor-immune interaction modeling

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