American Association for Cancer Research
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Supplementary Figure 2 from Cell Surface Delivery of TRAIL Strongly Augments the Tumoricidal Activity of T Cells

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posted on 2023-03-31, 16:24 authored by Marco de Bruyn, Yunwei Wei, Valerie R. Wiersma, Douwe F. Samplonius, Harry G. Klip, Ate G.J. van der Zee, Baofeng Yang, Wijnand Helfrich, Edwin Bremer

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ARTICLE ABSTRACT

Purpose: Adoptive T-cell therapy generally fails to induce meaningful anticancer responses in patients with solid tumors. Here, we present a novel strategy designed to selectively enhance the tumoricidal activity of T cells by targeted delivery of TNF-related apoptosis-inducing ligand (TRAIL) to the T-cell surface.Experimental Design: We constructed two recombinant fusion proteins, anti-CD3:TRAIL and K12:TRAIL. Tumoricidal activity of T cells in the presence of these fusion proteins was assessed in solid tumor cell lines, primary patient-derived malignant cells, and in a murine xenograft model.Results: When added to T cells, K12:TRAIL and anti-CD3:TRAIL selectively bind to the T-cell surface antigens CD3 and CD7, respectively, leading to cell surface accretion of TRAIL. Subsequently, anti-CD3:TRAIL and K12:TRAIL increased the tumoricidal activity of T cells toward cancer cell lines and primary patient-derived malignant cells by more than 500-fold. Furthermore, T-cell surface delivery of TRAIL strongly inhibited tumor growth and increased survival time of xenografted mice more than 6-fold.Conclusions: Targeted delivery of TRAIL to cell surface antigens of T cells potently enhances the tumoricidal activity of T cells. This approach may be generally applicable to enhance the efficacy of adoptive T-cell therapy. Clin Cancer Res; 17(17); 5626–37. ©2011 AACR.