A Bispecific Antibody Based on Pertuzumab Fab Has Potent Antitumor Activity

Wentong Deng1,2, Jiayu Liu1,2, Haitao Pan1,2

  • 1School of Pharmaceutical Sciences.

Insights

A novel bispecific antibody, Her2(Per)-S-Fab, effectively targets and reduces HER2-positive breast cancer tumors. This antibody demonstrates potent cytotoxicity, offering a promising new treatment alternative for patients with HER2-positive cancers.

Area of Science:

  • Oncology
  • Immunology
  • Biotechnology

Background:

  • Human epidermal growth factor receptor 2 (HER2) overexpression drives metastatic breast cancer progression.
  • Monoclonal antibodies like trastuzumab and pertuzumab are established HER2-targeted therapies, inhibiting HER2 signaling and mediating antibody-dependent cell-mediated cytotoxicity (ADCC).

Purpose of the Study:

  • To develop and evaluate a novel bispecific antibody, Her2(Per)-S-Fab, for enhanced HER2-positive cancer treatment.
  • To assess the efficacy of Her2(Per)-S-Fab in inhibiting tumor growth and mediating cytotoxicity.

Main Methods:

  • Generation of a bispecific antibody (Her2(Per)-S-Fab) by conjugating a pertuzumab fragment (Fab) to an anti-CD16 single domain antibody.
  • Efficient expression and purification of Her2(Per)-S-Fab using Escherichia coli.
  • In vitro and in vivo studies to evaluate the cytotoxic effects of Her2(Per)-S-Fab against HER2-positive tumor cells.

Main Results:

  • Her2(Per)-S-Fab was successfully expressed and purified from E. coli.
  • Demonstrated potent in vitro and in vivo cytotoxicity against HER2-positive tumor cells.
  • Indicated potential for enhanced anti-tumor activity compared to existing therapies.

Conclusions:

  • Her2(Per)-S-Fab is a viable bispecific antibody candidate for targeting HER2-positive cancers.
  • This novel antibody demonstrates significant anti-tumor efficacy, presenting a potential new therapeutic option.
  • Further investigation into Her2(Per)-S-Fab could lead to improved treatment strategies for HER2-positive breast cancer patients.

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