ArticleMolecular cancer therapeutics2024
HPN328, a Trispecific T Cell-Activating Protein Construct Targeting DLL3-Expressing Solid Tumors.
Article in Molecular cancer therapeutics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 21 citations in OpenAlex.
- Review
- Emerging Therapeutic Strategies in Small-Cell Lung Cancer: From Adaptive Resistance to Precision Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Single-Cell and Spatial Transcriptomics Reframe the Immunosuppressive Microenvironment of Neuroendocrine Neoplasms.Cancers · 2026Review
- Landscape of T-cell bispecific antibodies in cancer therapy: therapeutic strategies, challenges and future prospection.Molecular cancer · 2026Review
- Emerging evidence for sequencing and combining PSMA-based therapies in prostate cancer.Nature reviews. Urology · 2026Review
- Review
- Small Cell Lung Cancer Classification: Unraveling Heterogeneity to Enable Personalized Treatments.Cancer research · 2026Review
- Advances in Systemic Therapy for Metastatic Pancreatic Neuroendocrine Neoplasms.Current treatment options in oncology · 2026Review
- Structural and functional insights into CD3 bispecific antibodies targeting DLL3 in cancer immunotherapy.Medical oncology (Northwood, London, England) · 2026Article
- Preclinical Activity of the DLL3-Targeted T-cell Engager MK-6070 in Neuroendocrine Prostate Cancer.Molecular cancer therapeutics · 2026Article
- Immune cell engagers in lung cancer.Frontiers in immunology · 2026Review
- T-cell engagers in cancer immunotherapy: mechanisms, challenges, and future perspectives.Frontiers in immunology · 2026Review
- A review on toxicities of T-cell engager-based therapies in solid tumors.Therapeutic advances in medical oncology · 2026Review
- T-cell redirecting therapies in lung cancer - a comprehensive analysis of clinical trials.Frontiers in immunology · 2026Review
- Small cell lung cancer: from immunobiological mechanisms to clinical advances.Frontiers in immunology · 2026Review
- Revolutionizing cancer immunotherapy: T cell engagers beyond hematologic malignancies toward solid tumors.Frontiers in immunology · 2026Review
- Next-generation T cell engagers in oncology: Pharmacologic evolution from bispecific to trispecific antibodies.The Journal of pharmacology and experimental therapeutics · 2025Review
- Predicting the Pharmacokinetics of T-Cell Engagers as a Function of Target-Mediated Drug Disposition.Clinical and translational science · 2025Article
- What Is On the Horizon for the Diagnosis and Treatment of SCLC and Large Cell Neuroendocrine Cancer?JTO clinical and research reports · 2025Review
- Persistent lineage plasticity driving lung cancer development and progression.Clinical and translational medicine · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
29 authors at 2 institutions in 1 country.
Funding
Abstract
Delta-like ligand 3 (DLL3) is expressed in more than 70% of small cell lung cancers (SCLCs) and other neuroendocrine-derived tumor types. SCLC is highly aggressive, and limited therapeutic options lead to poor prognosis for patients. HPN328 is a trispecific T cell-activating construct (TriTAC) consisting of three binding domains: a CD3 binder for T-cell engagement, an albumin binder for half-life extension, and a DLL3 binder for tumor cell engagement. In vitro assays, rodent models, and non-human primates were used to assess the activity of HPN328. HPN328 induces potent dose-dependent killing of DLL3-expressing SCLC cell lines in vitro, concomitant with T-cell activation and cytokine release. In an NCI-H82 xenograft model with established tumors, HPN328 treatment led to T-cell recruitment and anti-tumor activity. In an immunocompetent mouse model expressing a human CD3ε epitope, mice previously treated with HPN328 withstood tumor rechallenge, demonstrating long-term anti-tumor immunity. When repeat doses were administered to cynomolgus monkeys, HPN328 was well tolerated up to 10 mg/kg. Pharmacodynamic changes, such as transient cytokine elevation, were observed, consistent with the expected mechanism of action of T-cell engagers. HPN328 exhibited linear pharmacokinetics in the given dose range with a serum half-life of 78 to 187 hours, supporting weekly or less frequent administration of HPN328 in humans. Preclinical and nonclinical characterization suggests that HPN328 is a highly efficacious, safe, and novel therapeutic candidate. A phase 1/2 clinical trial is currently underway testing safety and efficacy in patients with DLL3-expressing malignancies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.