Development of a leucine-rich repeat-containing protein 15-targeted radio-immunotheranostic approach to deplete pro-tumorigenic mechanisms and immunotherapy resistance.

ABSTRACT: 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 murine

SUBMITTER: Storey CM 

PROVIDER: S-EPMC12480655 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature