International Journal of Molecular Sciences (Nov 2022)

NKp44-Derived Peptide Used in Combination Stimulates Antineoplastic Efficacy of Targeted Therapeutic Drugs

  • Muhammed Iraqi,
  • Priyanka Bolel,
  • Rhitajit Sarkar,
  • Baisali Bhattacharya,
  • Muhammad Abu Ahmad,
  • Avishay Edri,
  • Laila C. Roisman,
  • Moshe Elkabets,
  • Walid Shalata,
  • Nir Peled,
  • Angel Porgador

DOI
https://doi.org/10.3390/ijms232214054
Journal volume & issue
Vol. 23, no. 22
p. 14054

Abstract

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Lung cancer cells in the tumor microenvironment facilitate immune evasion that leads to failure of conventional chemotherapies, despite provisionally decided on the genetic diagnosis of patients in a clinical setup. The current study follows three lung cancer patients who underwent “personalized” chemotherapeutic intervention. Patient-derived xenografts (PDXs) were subjected to tumor microarray and treatment screening with chemotherapies, either individually or in combination with the peptide R11-NLS-pep8; this peptide targets both membrane-associated and nuclear PCNA. Ex vivo, employing PDX-derived explants, it was found that combination with R11-NLS-pep8 stimulated antineoplastic effect of chemotherapies that were, although predicted based on the patient’s genetic mutation, inactive on their own. Furthermore, treatment in vivo of PDX-bearing mice showed an exactly similar trend in the result, corroborating the finding to be translated into clinical setup.

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