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CAR memory-like NK cells targeting the membrane proximal domain of mesothelin demonstrate promising activity in ovarian cancer. | LitMetric

AI Article Synopsis

  • Epithelial ovarian cancer (EOC) is a highly deadly gynecological cancer, but recent studies have shown that cytokine-induced memory-like (CIML) natural killer (NK) cells can effectively target EOC cells and enhance immune responses.
  • The research indicates that CIML NK cells not only increase activation receptor expression but also improve antitumor effects when engineered with a chimeric antigen receptor (CAR) aimed at mesothelin (MSLN) found on EOC cells.
  • These CAR-modified CIML NK cells significantly inhibited tumor growth and metastasis in animal models, suggesting they could be a promising new treatment approach for EOC patients.

Article Abstract

Epithelial ovarian cancer (EOC) remains one of the most lethal gynecological cancers. Cytokine-induced memory-like (CIML) natural killer (NK) cells have shown promising results in preclinical and early-phase clinical trials. In the current study, CIML NK cells demonstrated superior antitumor responses against a panel of EOC cell lines, increased expression of activation receptors, and up-regulation of genes involved in cell cycle/proliferation and down-regulation of inhibitory/suppressive genes. CIML NK cells transduced with a chimeric antigen receptor (CAR) targeting the membrane-proximal domain of mesothelin (MSLN) further improved the antitumor responses against MSLN-expressing EOC cells and patient-derived xenograft tumor cells. CAR arming of the CIML NK cells subtanstially reduced their dysfunction in patient-derived ascites fluid with transcriptomic changes related to altered metabolism and tonic signaling as potential mechanisms. Lastly, the adoptive transfer of MSLN-CAR CIML NK cells demonstrated remarkable inhibition of tumor growth and prevented metastatic spread in xenograft mice, supporting their potential as an effective therapeutic strategy in EOC.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11244547PMC
http://dx.doi.org/10.1126/sciadv.adn0881DOI Listing

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