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Therapeutic Antibody Targeting Tumor- and Osteoblastic Niche-Derived Jagged1 Sensitizes Bone Metastasis to

Hanqiu Zheng1, Yangjin Bae2, Sabine Kasimir-Bauer3

  • 1Department of Molecular Biology, Princeton University, Washington Road, LTL 255, Princeton, NJ 08544, USA.

Cancer Cell
|December 13, 2017
PubMed

Insights

A new antibody, 15D11, targets Jagged1 to combat breast cancer bone metastasis. It inhibits metastasis and enhances chemotherapy effectiveness by blocking tumor-stromal interactions.

Area of Science:

  • Oncology
  • Cancer Biology
  • Immunotherapy

Background:

  • Bone metastasis is a significant threat to breast cancer patients.
  • Tumor-derived Jagged1 mediates interactions between tumor and stromal cells, promoting osteolytic bone metastasis.
  • Osteoblast-derived Jagged1 also contributes to bone metastasis by creating a survival niche for cancer cells.

Purpose of the Study:

  • To develop a fully human monoclonal antibody targeting Jagged1 for breast cancer bone metastasis.
  • To evaluate the efficacy of the anti-Jagged1 antibody (15D11) in preventing and treating bone metastasis.
  • To investigate the role of osteoblast-derived Jagged1 in bone metastasis.

Main Methods:

  • Development of a fully human monoclonal antibody against Jagged1 (clone 15D11).
  • In vitro and in vivo studies to assess the inhibitory effect of 15D11 on bone metastasis.
  • Chemotherapy sensitization assays.
  • Generation and utilization of an osteoblast-specific Jagged1 transgenic mouse model.

Main Results:

  • The monoclonal antibody 15D11 effectively inhibits bone metastasis of Jagged1-expressing breast cancer cells.
  • 15D11 significantly sensitizes bone metastasis to chemotherapy by blocking Jagged1-induced osteoblast survival niches.
  • Osteoblast-specific Jagged1 was confirmed to promote bone metastasis.

Conclusions:

  • The fully human monoclonal antibody 15D11 is a promising therapeutic agent for breast cancer bone metastasis.
  • 15D11 offers a dual mechanism of action: direct inhibition of metastasis and enhancement of chemotherapy efficacy.
  • Targeting Jagged1, including osteoblast-derived Jagged1, represents a viable strategy for managing bone metastasis in breast cancer.
Keywords:
Jagged1bone metastasisbreast cancerchemoresistanceneutralizing antibodyosteoblastic nicheosteoblasts

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