Mild hyperthermia influence on Herceptin (R) properties

JM Escoffre, RHR Deckers, Noboru Sasaki, Clemens Bos, Chrit Moonen

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background. Mild hyperthermia (mHT) increases the tumor perfusion and vascular permeability, and reduces the interstitial fluid pressure, resulting in better intra-tumoral bioavailability of low molecular weight drugs. This approach is potentially also attractive for delivery of therapeutic macromolecules, such as antibodies. Here, we investigated the effects of mHT on the stability, immunological and pharmacological properties of Herceptin (R), a clinically approved antibody, targeting the human epidermal growth factor receptor 2 (HER-2) overexpressed in breast cancer.

Results. Herceptin (R) was heated to 37 degrees C (control) and 42 degrees C (mHT) for 1 hour. Formation of Herceptin (R) aggregates was measured using Nile Red assay. mHT did not result in additional Herceptin (R) aggregates compared to 37 degrees C, showing the Herceptin (R) stability is unchanged. Immunological and pharmacological properties of Herceptin (R) were evaluated following mHT using HER-2 positive breast cancer cells (BT-474). Exposure of Herceptin (R) to mHT preserved recognition and binding affinity of Herceptin (R) to HER-2. Western-blot and cell proliferation assays on BT-474 cells showed that mHT left the inhibitory activities of Herceptin (R) unchanged.

Conclusions. The stability, and the immunological and pharmacological properties of Herceptin (R) are not negatively affected by mHT. Further in-vivo studies are required to evaluate the influence of mHT on intra-tumoral bioavailability and therapeutic effectiveness of Herceptin (R).

Original languageEnglish
Pages (from-to)41-49
Number of pages9
JournalRadiology and oncology
Volume49
Issue number1
DOIs
Publication statusPublished - Mar 2015

Keywords

  • mild hyperthermia
  • anticancer antibody
  • Herceptin (R)
  • breast cancer
  • METASTATIC BREAST-CANCER
  • MONOCLONAL-ANTIBODIES
  • LOCAL HYPERTHERMIA
  • NANOPARTICLE EXTRAVASATION
  • ANTIGEN-EXPRESSION
  • TUMOR UPTAKE
  • TRASTUZUMAB
  • XENOGRAFTS
  • DELIVERY
  • CHEMOTHERAPY

Fingerprint

Dive into the research topics of 'Mild hyperthermia influence on Herceptin (R) properties'. Together they form a unique fingerprint.

Cite this