Trop-2 is a novel target for solid cancer therapy with sacituzumab govitecan (IMMU-132), an antibody-drug conjugate (ADC)

Oncotarget. 2015 Sep 8;6(26):22496-512. doi: 10.18632/oncotarget.4318.


Trop-2 is a novel target for ADC therapy because of its high expression by many solid cancers. The rational development of IMMU-132 represents a paradigm shift as an ADC that binds a well-known moderately-cytotoxic drug, SN-38, to the anti-Trop-2 antibody. In vitro and in vivo studies show enhanced efficacy, while there is a gradual release of SN-38 that contributes to the overall effect. IMMU-132 is most efficacious at a high drug:antibody ratio (DAR) of 7.6:1, which does not affect binding and pharmacokinetics. It targets up to 136-fold more SN-38 to a human cancer xenograft than irinotecan, SN-38's prodrug. IMMU-132 delivers SN-38 in its most active, non-glucuronidated form, which may explain the lower frequency of severe diarrhea than with irinotecan. Thus, this ADC, carrying a moderately-toxic drug targeting Trop-2 represents a novel cancer therapeutic that is showing promising activity in patients with several metastatic cancer types, including triple-negative breast cancer, non-small-cell and small-cell lung cancers.

Keywords: SN-38; Trop-2; antibody-drug conjugate; solid cancers; triple-negative breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / immunology
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Antigens, Neoplasm / biosynthesis
  • Antigens, Neoplasm / immunology*
  • Camptothecin / analogs & derivatives*
  • Camptothecin / immunology
  • Camptothecin / pharmacology
  • Cell Adhesion Molecules / biosynthesis
  • Cell Adhesion Molecules / immunology*
  • Cell Line, Tumor
  • Female
  • Humans
  • Immunoconjugates / immunology
  • Immunoconjugates / pharmacology*
  • Irinotecan
  • MCF-7 Cells
  • Mice, Nude
  • Molecular Targeted Therapy
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / immunology
  • Xenograft Model Antitumor Assays


  • Antibodies, Monoclonal, Humanized
  • Antigens, Neoplasm
  • Cell Adhesion Molecules
  • Immunoconjugates
  • TACSTD2 protein, human
  • Irinotecan
  • sacituzumab govitecan
  • Camptothecin