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Tissue factor-targeted immunotherapy of melanoma and triple negative breast cancer using a second generation ICON
© Hu et al. 2015
Published: 4 November 2015
L-ICON protein and adenoviral vectors have been developed by recombinant DNA techniques. The binding activity of L-ICON to human melanoma lines with or without BRAF mutant and to human TNBC was assayed by flow cytometry and cell ELISA. Its ADCC effect was determined by an ADCC effector assay (Promega). L-ICON therapy of TNBC via intra-lesional injection of Ad-L-ICON was compared to Ad-ICON in a nude mouse model of TNBC MDA-MB-231.
The molecular weight of L-ICON was 100 kDa (Fig. 1), only 50% of ICON's. L-ICON could bind to human and canine melanoma lines, regardless of their BRAF status. L-ICON could also bind to human TNBC lines, similarly to the first generation ICON. L-ICON could mediate ADCC effect to these cancer cells in vitro. Intra-lesional L-ICON and ICON immunotherapy via adenoviral vectors were similarly effective for the treatment of human TNBC in a nude mouse model.
L-ICON molecular mass was reduced significantly while its binding activity to cancer cells was intact. L-ICON therapy was effective for the treatment of melanoma and TNBC in vitro and in vivo in a preclinical mouse model.
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