Antibody–Drug Conjugates for the Treatment of Solid Tumors: Clinical Experience and Latest Developments

Aiko Nagayama, Leif W. Ellisen, Bruce Chabner, Aditya Bardia

Research output: Contribution to journalReview article

17 Citations (Scopus)

Abstract

Antibody–drug conjugates (ADCs) are complex immunoconjugates designed to selectively deliver toxic small molecules preferentially to cancer cells. These immunoconjugates consist of a monoclonal antibody - directed to a tumor antigen - and a cytotoxic agent that is conjugated to the antibody via a molecular linker. Following the binding to a specific antigen on the surface of cancer cells, the conjugate is internalized and releases its cytotoxic payload to kill the malignant cell. ADCs that have gained regulatory approval from the US Food and Drug Administration (FDA) include brentuximab vedotin for CD30-positive Hodgkin’s lymphoma and trastuzumab emtansine for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Several other agents are in advanced stages of clinical development, including sacituzumab govitecan for breast cancer, mirvetuximab soravtansine for ovarian cancer, rovalpituzumab tesirine for lung cancer, depatuxizumab mafodotin for glioblastoma, and oportuzumab monatox for bladder cancer. This review provides an overview of the recent clinical experience with the approved, most advanced, and other promising candidates of ADCs for solid tumors, including a description of biology and chemistry of ADCs, drug resistance and biomarkers, and the future perspective on combination strategies with these new immunoconjugates.

Original languageEnglish
Pages (from-to)719-739
Number of pages21
JournalTargeted Oncology
Volume12
Issue number6
DOIs
Publication statusPublished - 2017 Dec 1
Externally publishedYes

Fingerprint

Immunoconjugates
Breast Neoplasms
Neoplasms
Poisons
Cytotoxins
Neoplasm Antigens
United States Food and Drug Administration
Glioblastoma
Surface Antigens
Hodgkin Disease
Drug Resistance
Urinary Bladder Neoplasms
Ovarian Neoplasms
Lung Neoplasms
Biomarkers
Monoclonal Antibodies
Antibodies

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Pharmacology (medical)

Cite this

Antibody–Drug Conjugates for the Treatment of Solid Tumors : Clinical Experience and Latest Developments. / Nagayama, Aiko; Ellisen, Leif W.; Chabner, Bruce; Bardia, Aditya.

In: Targeted Oncology, Vol. 12, No. 6, 01.12.2017, p. 719-739.

Research output: Contribution to journalReview article

Nagayama, Aiko ; Ellisen, Leif W. ; Chabner, Bruce ; Bardia, Aditya. / Antibody–Drug Conjugates for the Treatment of Solid Tumors : Clinical Experience and Latest Developments. In: Targeted Oncology. 2017 ; Vol. 12, No. 6. pp. 719-739.
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