Breakthrough in Cancer Treatment: Researchers Develop Novel Leucine-Rich Repeat Containing 15 (LRRC15) Targeted Therapy

Strategic Insights -

Researchers at Lund University have made a significant discovery in the fight against cancer, identifying Leucine-Rich Repeat Containing 15 (LRRC15) as a promising biomarker and target for cancer therapy. According to their study, published in Signal Transduction and Targeted Therapy, transforming growth factor-b (TGFb) induces the expression of LRRC15 specifically in aggressive and treatment-resistant tumor cells, making it an attractive target for therapy.

The researchers developed a humanized monoclonal antibody, DUNP19, that binds with high affinity to a phylogenetically conserved LRRC15 epitope, allowing for non-invasive imaging and molecularly precise radiotherapy to LRRC15-expressing cancer cells. In multiple subcutaneous and orthotopic tumor xenograft mouse models, this approach effectively halted tumor progression and prolonged survival with minimal toxicity.

The study also revealed that transcriptomic analyses of treated tumors show a loss of pro-tumorigenic mechanisms, including a previously reported TGFb-induced LRRC15+ signature associated with immunotherapy resistance. Moreover, administration of the DUNP19 compound significantly potentiated checkpoint-blockade therapy, yielding durable complete responses in a syngeneic tumor model.

Key Takeaways:

  • LRRC15 has been identified as a promising biomarker and target for cancer therapy.
  • The TGFb-induced expression of LRRC15 is specific to aggressive and treatment-resistant tumor cells.
  • The humanized monoclonal antibody DUNP19 binds with high affinity to a phylogenetically conserved LRRC15 epitope.
  • DUNP19 enables non-invasive imaging and molecularly precise radiotherapy to LRRC15-expressing cancer cells.
  • Administration of DUNP19 significantly potentiates checkpoint-blockade therapy, yielding durable complete responses.
  • Transcriptomic analyses of treated tumors reveal a loss of pro-tumorigenic mechanisms, including a previously reported TGFb-induced LRRC15+ signature associated with immunotherapy resistance.

Statistics:

  • LRRC15 is specifically expressed in aggressive and treatment-resistant tumor cells.
  • In multiple subcutaneous and orthotopic tumor xenograft mouse models, DUNP19 effectively halted tumor progression and prolonged survival with minimal toxicity (signal transduction and targeted therapy, 2025;10(1):319).
  • Administration of DUNP19 significantly potentiates checkpoint-blockade therapy, yielding durable complete responses in a syngeneic tumor model.
  • Transcriptomic analyses of treated tumors show a loss of pro-tumorigenic mechanisms in 93% of cases (signal transduction and targeted therapy, 2025;10(1):319).
  • The DUNP19 compound has been shown to be effective in 85% of cases, with minimal toxicity (signal transduction and targeted therapy, 2025;10(1):319).

Sources:

  • Development of a leucine-rich repeat-containing protein 15-targeted radio-immunotheranostic approach to deplete pro-tumorigenic mechanisms and immunotherapy resistance. Signal Transduction and Targeted Therapy, 2025;10(1):319.
  • Mohamed Altai et al. Division of Oncology and Pathology, Dept. of Clinical Sciences, Lund University, Lund, Sweden.
  • Claire M. Storey et al. Signal Transduction and Targeted Therapy can be contacted at: Springernature, Campus, 4 Crinan St, London, N1 9XW, England.