biostudies-literatureUnknown10(1)Storey CMLeucine-rich repeat containing 15 (LRRC15) has emerged as an attractive biomarker and target for cancer therapy. Transforming growth factor-β (TGFβ) induces the expression of this plasma membrane protein specifically in aggressive and treatment resistant tumor cells derived from mesenchymal stem cells, with minimal expression observed in non-neoplastic tissues. We have developed a humanized monoclonal antibody, DUNP19, that specifically binds with high affinity to a phylogenetically conserved LRRC15 epitope and is rapidly internalized upon LRRC15 binding. In multiple subcutaneous and orthotopic tumor xenograft mouse models, Lutetium-177 labeled DUNP19 ([¹⁷⁷Lu]Lu-DUNP19) enabled non-invasive imaging and molecularly precise radiotherapy to LRRC15-expressing cancer cells and murineSignal transduction and targeted therapy319https://www.ebi.ac.uk/biostudies/studies/S-EPMC12480655biostudies-literatureDevelopment of a leucine-rich repeat-containing protein 15-targeted radio-immunotheranostic approach to deplete pro-tumorigenic mechanisms and immunotherapy resistance.PMC12480655Thorek DTrajkovic-Arsic MMao LAltai MAbou DSubudhi SKCheng MUlmert DLamminmaki UUlmert ERidley AHerrmann KDamoiseaux RFederman NZedan WPark JSiveke JStorey CMZhu HCzernin JHasson AGraeber TGMarks HYang XBreuer LSiddiqui BALuckerath KSafi MYuen CGeres SBentolila LfalseDevelopment of a leucine-rich repeat-containing protein 15-targeted radio-immunotheranostic approach to deplete pro-tumorigenic mechanisms and immunotherapy resistance.Leucine-rich repeat containing 15 (LRRC15) has emerged as an attractive biomarker and target for cancer therapy. Transforming growth factor-β (TGFβ) induces the expression of this plasma membrane protein specifically in aggressive and treatment resistant tumor cells derived from mesenchymal stem cells, with minimal expression observed in non-neoplastic tissues. We have developed a humanized monoclonal antibody, DUNP19, that specifically binds with high affinity to a phylogenetically conserved LRRC15 epitope and is rapidly internalized upon LRRC15 binding. In multiple subcutaneous and orthotopic tumor xenograft mouse models, Lutetium-177 labeled DUNP19 ([¹⁷⁷Lu]Lu-DUNP19) enabled non-invasive imaging and molecularly precise radiotherapy to LRRC15-expressing cancer cells and murine2025-01-01T00:00:00Z2025 Sep2026-06-03T22:50:46.541Z2026-05-02T03:11:45.625ZS-EPMC124806554102270410.1038/s41392-025-02410-9