Modular delivery of co-stimulatory signals through a PD-1-based immunoswitch receptor improves the functionality of Hepatitis B Virus-specific engineered T cells - Report - MDSpire

Modular delivery of co-stimulatory signals through a PD-1-based immunoswitch receptor improves the functionality of Hepatitis B Virus-specific engineered T cells

  • By

  • Luis Felipe Olguín-Contreras

  • Johanna Heep

  • Lisa Schiller

  • Eva Loffredo-Verde

  • Marvin M. Festag

  • Kai Metzger

  • Stephanie Färber

  • Merve Gültan

  • Margaret Tulessin

  • Susanne Wilde

  • Karin Wisskirchen

  • Elfriede Noessner

  • Ulrike Protzer

  • July 3, 2026

  • 0 min

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Clinical Report: Enhanced Functionality of Engineered T Cells Targeting HBV

Overview

This study presents a novel approach using PD-1-based immunoswitch receptors to enhance the functionality of engineered T cells targeting hepatitis B virus (HBV). The findings indicate that this method improves T-cell activity and persistence in a chronic infection context.

Background

Chronic hepatitis B virus infection affects over 250 million people worldwide and is a leading cause of hepatocellular carcinoma. The virus's ability to evade immune clearance poses significant challenges for effective treatment, necessitating innovative therapeutic strategies. Engineered T-cell therapies have emerged as promising options to restore antiviral immunity, yet their efficacy is often limited by the immunosuppressive liver microenvironment.

Data Highlights

No numerical data provided in the source material.

Key Findings

  • PD-1-based immunoswitch receptors enhance T-cell sensitivity and cytotoxicity against HBV.
  • Signal stacking of additional co-stimulatory domains did not improve second-generation S-CAR functionality.
  • PD-1_4-1BB receptor demonstrated superior ability to induce sustained NF-κB signaling.
  • In vivo studies showed improved T-cell persistence and reduced TOX upregulation with PD-1_4-1BB.
  • Modular co-stimulation via immunoswitch receptors offers a versatile platform for T-cell therapies in chronic infections.

Clinical Implications

The development of PD-1-based immunoswitch receptors may provide a new avenue for enhancing the effectiveness of engineered T-cell therapies in chronic hepatitis B.

Conclusion

PD-1-based immunoswitch receptors represent a promising strategy to enhance engineered T-cell responses against HBV.

Related Resources & Content

  1. Gut — Engineered virus-hunter vaccine overcomes HBV immune tolerance
  2. Blood Cancer Journal — The stimulation of PD-L1-specific cytotoxic T lymphocytes can both directly and indirectly enhance antileukemic immunity
  3. Blood Cancer Journal — Enhancing the Efficacy of Anti-CD19 and Anti-CD22 CAR T-Cells with PD-1-CD28 Checkpoint Fusion Proteins
  4. AASLD Announces New Practice Guideline on Treatment of Chronic Hepatitis B | AASLD
  5. Frontiers in Immunology — Target receptor expression dictates the selective intra-tumoral targeting of CD8+ T cells by eciskafusp alfa in matched PBMCs and TILs from CPI-naïve patients
  6. Clinical results of an HBV-specific T-cell receptor-T-cell therapy (SCG101) in patients with HBV-related hepatocellular carcinoma treated in an investigator-initiated, interventional trial - PMC
  7. Twenty-four-week anti-PD-1 antibody regimen promoted HBsAg reduction and concurrently enhanced HBV-specific T cell responses in patients with chronic hepatitis B
  8. AASLD Announces New Practice Guideline on Treatment of Chronic Hepatitis B | AASLD

Original Source(s)

Modular delivery of co-stimulatory signals through a PD-1-based immunoswitch receptor improves the functionality of Hepatitis B Virus-specific engineered T cells

  • by Luis Felipe Olguín-Contreras, Johanna Heep, Lisa Schiller, Eva Loffredo-Verde, Marvin M. Festag, Kai Metzger, Stephanie Färber, Merve Gültan, Margaret Tulessin, Susanne Wilde, Karin Wisskirchen, Elfriede Noessner, Ulrike Protzer

  • July 3, 2026

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