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Novel trispecific killer engager targeting B7-H3 enhances natural killer cell antitumor activity against head and neck cancer

  • 0University of Minnesota Masonic Cancer Center, Minneapolis, Minnesota, USA.
Journal for Immunotherapy of Cancer +

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July 24, 2025

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July 24, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

A novel trispecific engager (TriKE) therapy targeting B7-H3 shows promise for head and neck squamous cell carcinoma (HNSCC). This therapy enhances natural killer (NK) cell activity against tumors, even in low-oxygen environments, improving survival in preclinical models.

Area Of Science

  • Immunology
  • Oncology
  • Biotechnology

Background

  • Head and neck squamous cell carcinoma (HNSCC), especially human papillomavirus-negative (HPV⁻) types, has a poor prognosis.
  • Patients with Fanconi anemia (FA) have a significantly higher risk of developing HNSCC.
  • Current immunotherapies are often ineffective due to the suppressive tumor microenvironment (TME).

Purpose Of The Study

  • To develop and evaluate a novel trispecific engager (TriKE) therapy targeting B7-H3 for HNSCC treatment.
  • To assess the efficacy of the TriKE in overcoming the hypoxic TME and enhancing natural killer (NK) cell activity.
  • To investigate the therapeutic potential of the B7H3 TriKE in preclinical models of HNSCC.

Main Methods

  • Generation of a B7H3 TriKE using a mammalian expression system.
  • Evaluation of NK cell degranulation, cytokine production, proliferation, and cytotoxicity assays.
  • Assessment of tumor killing under acute and prolonged hypoxia (1% oxygen) in vitro and in vivo using human HNSCC xenografts in NSG mice.

Main Results

  • High B7-H3 expression in HPV⁻ HNSCC correlates with poor survival.
  • The B7H3 TriKE enhanced NK cell activation, expansion, and cytotoxicity in HPV⁻ HNSCC patients and healthy donors.
  • The TriKE demonstrated potent anti-tumor activity and improved survival in vivo, overcoming hypoxic suppression of NK cells.

Conclusions

  • The B7H3 TriKE represents a novel immunotherapy capable of overcoming hypoxic suppression of NK cells in the HNSCC TME.
  • This innovative therapy shows significant translational potential for patients with HNSCC.
  • Further development for clinical application is warranted.

Keywords:

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