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Published on: June 2, 2022

Selective inhibition of matrix metalloproteinase-14 blocks tumor growth, invasion, and angiogenesis

Laetitia Devy1, Lili Huang, Laurent Naa

  • 1Dyax Corp, Cambridge, Massachusetts 02139, USA. ldevy@dyax.com

Cancer Research
|February 12, 2009
PubMed

Insights

A novel antibody, DX-2400, selectively inhibits matrix metalloproteinase-14 (MMP-14), a key driver of tumor growth and metastasis. This targeted approach shows promise for treating solid tumors by blocking angiogenesis and tumor progression.

Area of Science:

  • Oncology
  • Biochemistry
  • Immunology

Background:

  • Matrix metalloproteinases (MMPs) are implicated in cancer progression.
  • MMP-14 (matrix metalloproteinase-14) plays a critical role in tumor growth, invasion, and angiogenesis.
  • MMP-14 also activates proMMP-2, amplifying pericellular proteolytic activity.

Purpose of the Study:

  • To investigate the role of MMP-14 in tumor growth and angiogenesis.
  • To evaluate the therapeutic potential of a selective MMP-14 inhibitor, DX-2400.

Main Methods:

  • Utilized DX-2400, a fully human MMP-14 inhibitory antibody developed via phage display.
  • Assessed the effect of DX-2400 on proMMP-2 processing in tumor and endothelial cells.
  • Evaluated the impact of DX-2400 on angiogenesis, tumor progression, and metastasis in vivo.

Main Results:

  • DX-2400 effectively blocked proMMP-2 processing.
  • The antibody inhibited angiogenesis and slowed tumor progression.
  • DX-2400 reduced the formation of metastatic lesions.

Conclusions:

  • Selective inhibition of MMP-14 is a viable non-cytotoxic cancer therapy strategy.
  • DX-2400 demonstrates potent, selective, and in vivo efficacy against solid tumors.
  • Targeting MMP-14 holds significant therapeutic potential for solid tumor treatment.

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