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

Int J Mol Sci. 2022 Nov 14;23(22):14054. doi: 10.3390/ijms232214054.

Abstract

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.

Keywords: NKp44; PCNA-binding peptide; lung cancer; personalized medicine; synergistic effect; tumor xenograft.

MeSH terms

  • Animals
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Disease Models, Animal
  • Drug Delivery Systems
  • Humans
  • Lung Neoplasms* / drug therapy
  • Mice
  • Peptides / pharmacology
  • Tumor Microenvironment

Substances

  • Peptides
  • Antineoplastic Agents