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Fig. 1 | Molecular Cancer

Fig. 1

From: Antibody-mediated delivery of a viral MHC-I epitope into the cytosol of target tumor cells repurposes virus-specific CD8+ T cells for cancer immunotherapy

Fig. 1

TEDbody-mediated CMV-pMHCI presentation drives efficient killing of target tumor cells by CMVp-CTLs. A Schematic of the TEDbody engineered for cytosolic delivery of an MHC-I-restricted viral CTL epitope peptide into the cytosol of target tumor cells. B Design of the TEDbodies carrying various CMVp495–503-encompassing peptides tested in this study and their nomenclature. A panel of CMVp495–503-encompassing peptides with N-terminally or N/C-extended sequences that were fused to the C-terminus of the heavy chain of inCT via an uncleavable 5-mer G4S linker. C A representative flow cytometric histogram of CMV-pMHCI display on the surface of cells as a consequence of extracellular treatment with the indicated synthetic peptide, TEDbody, or control Ab, as detected by the CMV-pMHCI-specific C1–17 Ab (red), compared to the control that used only the secondary Ab (blue). D Fold changes in the gMFI of CMV-pMHCI display, as determined by normalization to gMFI of the control involving only the secondary Ab. In (C) and (D), the indicated cells were treated with the indicated synthetic peptide, TEDbody, or control Ab (4 μM) at 4 °C for 3 h or at 37 °C for 18 h followed by flow cytometric analysis. All flow cytometric data for MDA-MB-231, LoVo, and NCI-H889 cells are shown in Fig. S3. In (D), bar graphs present the mean ± SEM (n ≥ 3). **P < 0.01 and ***P < 0.001 compared with HPVE11–19-treated cells for CMV pp65-derived peptides or compared with inCT-treated cells for the TEDbody/control Ab. E Percentage rates of tumor cell lysis by ex vivo-expanded CMVp-CTLs for integrin αvβ5+ HLA-A*02:01+ MDA-MB-231 cells, integrin αvβ5+ HLA-A*02:01− LoVo cells, and integrin αvβ5− HLA-A*02:01+ NCI-H889 cells, treated with the indicated synthetic peptide, TEDbody, or control Ab (0.2 or 1.0 μM) at 37 °C for 12 h prior to coculture with CMVp-CTLs for 18 h at an E:T ratio of 5:1. Percentage rates of lysis were determined by LDH quantification in the supernatant. The bar graphs present the mean ± SEM (n = 3)

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