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

Wu, Zherui; Fournel, Ludovic; Stadler, Nicolas; Liu, Jin; Boullier, Agnès; Hoyeau, Nadia; Fléjou, Jean François; Duchatelle, Véronique; Djebrani-Oussedik, Nouzha and Agopiantz, Mikaël, et al. (2019) In Cancer Letters 444. p.147-161
Abstract

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).... (More)

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.

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@article{0ccee0f0-49b3-4ea5-92f8-6eeb7b019149,
  abstract     = {<p>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.</p>},
  author       = {Wu, Zherui and Fournel, Ludovic and Stadler, Nicolas and Liu, Jin and Boullier, Agnès and Hoyeau, Nadia and Fléjou, Jean François and Duchatelle, Véronique and Djebrani-Oussedik, Nouzha and Agopiantz, Mikaël and Ségal-Bendirdjian, Evelyne and Gompel, Anne and Alifano, Marco and Melander, Olle and Trédaniel, Jean and Forgez, Patricia},
  issn         = {0304-3835},
  keyword      = {Advanced lung cancer,Anti-tumor drug,Neurotensin antibody,Restoration of platinum salt-based chemotherapy sensitivity,Tumor cell plasticity},
  language     = {eng},
  pages        = {147--161},
  publisher    = {Elsevier},
  series       = {Cancer Letters},
  title        = {Modulation of lung cancer cell plasticity and heterogeneity with the restoration of cisplatin sensitivity by neurotensin antibody},
  url          = {http://dx.doi.org/10.1016/j.canlet.2018.12.007},
  volume       = {444},
  year         = {2019},
}