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Olle Melander

Principal investigator

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Modulation of lung cancer cell plasticity and heterogeneity with the restoration of cisplatin sensitivity by neurotensin antibody

Author

  • Zherui Wu
  • Ludovic Fournel
  • Nicolas Stadler
  • Jin Liu
  • Agnès Boullier
  • Nadia Hoyeau
  • Jean François Fléjou
  • Véronique Duchatelle
  • Nouzha Djebrani-Oussedik
  • Mikaël Agopiantz
  • Evelyne Ségal-Bendirdjian
  • Anne Gompel
  • Marco Alifano
  • Olle Melander
  • Jean Trédaniel
  • Patricia Forgez

Summary, in English

Overall survival of patients with metastatic non-small cell lung cancer (NSCLC) has significantly improved with platinum-based salt treatments and recently with targeted therapies and immunotherapies. However, treatment failure occurs due to acquired or emerging tumor resistance. We developed a monoclonal antibody against the proform of neurotensin (LF-NTS mAb) that alters the homeostasis of tumors overexpressing NTSR1. Neurotensin is frequently overexpressed along with its high affinity receptor (NTSR1) in tumors from epithelial origins. This ligand/receptor complex contributes to the progression of many tumor types by activation of the cellular effects involved in tumor progression (proliferation, survival, migration, and invasion). We demonstrate that LF-NTS mAb operates on the plasticity of tumor cells overexpressing NTSR1 and lowers their aggressiveness. The mAb enables the restoration of platinum-based therapies responsiveness, while also decreasing metastatic processes. Efficacy dosage with long-term treatment showed no obvious adverse events, while demonstrating improvement in the performance status. Our data suggests that LF-NTS mAb is an ideal candidate to be safely added to the conventional standard of care in order to improve its efficacy.

Department/s

  • Cardiovascular Research - Hypertension
  • EpiHealth: Epidemiology for Health
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year

2019

Language

English

Pages

147-161

Publication/Series

Cancer Letters

Volume

444

Document type

Journal article

Publisher

Elsevier

Topic

  • Cancer and Oncology

Keywords

  • Advanced lung cancer
  • Anti-tumor drug
  • Neurotensin antibody
  • Restoration of platinum salt-based chemotherapy sensitivity
  • Tumor cell plasticity

Status

Published

Research group

  • Cardiovascular Research - Hypertension

ISBN/ISSN/Other

  • ISSN: 0304-3835