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A bispecific anti-ErbB2 antibody potently induces ErbB2 internalization and suppresses ErbB2-overexpressing tumor

Yajun Zhang1, Lingfei Wang1, Xiaodan Chong1

  • 1International Joint Cancer Institute, The Second Military Medical University, Shanghai, 200433, People's Republic of China.

Biochemical and Biophysical Research Communications
|July 2, 2016
PubMed

Insights

A novel bispecific antibody, TPL, effectively targets ErbB2-positive gastric cancer by potently down-regulating ErbB2. This antibody shows greater antitumor effects than combined therapies, offering a promising new treatment strategy.

Area of Science:

  • Oncology
  • Immunotherapy
  • Molecular Biology

Background:

  • Trastuzumab is approved for ErbB2-positive gastric cancer, but its efficacy is variable.
  • Improving ErbB2-targeting therapy is crucial due to modest efficacy of current treatments.
  • Monoclonal antibody-induced receptor down-regulation enhances antitumor effects.

Purpose of the Study:

  • To investigate the ErbB2 internalization-inducing ability of non-competitive anti-ErbB2 monoclonal antibody (mAb) combinations.
  • To evaluate the efficacy of a novel bispecific antibody (TPL) engineered from trastuzumab and pertuzumab.
  • To assess TPL's potential as a treatment for ErbB2-overexpressing gastric cancer.

Main Methods:

  • Screening of 18 non-competitive anti-ErbB2 mAb pairs for ErbB2 internalization.
  • Evaluating ErbB2 down-regulation by trastuzumab, pertuzumab, and the bispecific antibody TPL.
  • Comparing the antitumor effects of TPL versus trastuzumab plus pertuzumab on gastric cancer cell lines.

Main Results:

  • Most non-competitive anti-ErbB2 mAb combinations did not induce significant ErbB2 down-regulation.
  • Only 4 out of 18 non-competitive mAb pairs efficiently induced ErbB2 internalization.
  • TPL potently down-regulated ErbB2 and showed superior antitumor activity compared to trastuzumab plus pertuzumab.

Conclusions:

  • The bispecific antibody TPL demonstrates potent ErbB2 down-regulation and significant antitumor efficacy in gastric cancer models.
  • TPL represents a promising therapeutic agent for ErbB2-overexpressing gastric cancer, potentially overcoming limitations of existing therapies.
  • Targeted ErbB2 internalization via bispecific antibodies offers a novel strategy for enhancing cancer treatment.
Keywords:
Bispecific antibodyDown-regulationErbB2Gastric cancerMonoclonal antibody

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