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Cell surface delivery of TRAIL strongly augments the tumoricidal activity of T cells

Marco de Bruyn1, Yunwei Wei, Valerie R Wiersma

  • 1Department of Surgery, Surgical Research Laboratories, University Medical Center Groningen (UMCG), University of Groningen, Groningen, The Netherlands.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|July 15, 2011
PubMed
Abstract

Insights

This study enhances adoptive T-cell therapy by engineering T cells to display TNF-related apoptosis-inducing ligand (TRAIL) on their surface. This novel approach significantly boosts T-cell anticancer activity against solid tumors.

Area of Science:

  • Immunology
  • Oncology
  • Biotechnology

Background:

  • Adoptive T-cell therapy often shows limited efficacy against solid tumors.
  • Enhancing T-cell tumoricidal activity is crucial for improving cancer treatment outcomes.

Purpose of the Study:

  • To develop a novel strategy for enhancing T-cell anticancer activity.
  • To selectively deliver TNF-related apoptosis-inducing ligand (TRAIL) to the T-cell surface.

Main Methods:

  • Construction of recombinant fusion proteins: anti-CD3:TRAIL and K12:TRAIL.
  • Assessment of T-cell tumoricidal activity against solid tumor cell lines, primary patient-derived malignant cells, and in a murine xenograft model.

Main Results:

  • Fusion proteins selectively bind to T-cell surface antigens, leading to TRAIL cell surface display.
  • T-cell tumoricidal activity increased >500-fold against cancer cell lines and primary malignant cells.
  • T-cell surface TRAIL delivery significantly inhibited tumor growth and improved survival in a xenograft model.

Conclusions:

  • Targeted T-cell surface delivery of TRAIL potently enhances T-cell tumoricidal activity.
  • This strategy holds promise for improving the efficacy of adoptive T-cell therapy for solid tumors.

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