1. High-efficiency lysis of cervical cancer by allogeneic NK cells derived from umbilical cord progenitors is independent of HLA status
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Ekaterina S. Jordanova, Hans van Vliet, A. Marijne Heeren, Daniëlle A.M. Heideman, Henk M.W. Verheul, Gemma G. Kenter, Jan Spanholtz, Tanja D. de Gruijl, John P. Veluchamy, Jaap D. H. van Eendenburg, AII - Cancer immunology, CCA - Cancer biology and immunology, Obstetrics and Gynaecology, Other departments, Amsterdam Reproduction & Development (AR&D), Cancer Center Amsterdam, Medical oncology laboratory, CCA - Cancer immunology, Obstetrics and gynaecology, Pathology, and Medical oncology
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0301 basic medicine ,Adoptive cell transfer ,Cancer Research ,Immunology ,Uterine Cervical Neoplasms ,Human leukocyte antigen ,Biology ,Adoptive NK immunotherapy ,Peripheral blood NK cells ,03 medical and health sciences ,Interleukin 21 ,0302 clinical medicine ,HLA Antigens ,Cell Line, Tumor ,Humans ,Transplantation, Homologous ,Cytotoxic T cell ,Immunology and Allergy ,Progenitor cell ,Receptor ,Lymphokine-activated killer cell ,Hematopoietic Stem Cell Transplantation ,Fetal Blood ,NKG2D ,CET ,3. Good health ,Killer Cells, Natural ,Phenotype ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cervical cancer ,NK ligands and receptors ,Female ,Original Article ,Immunotherapy ,Umbilical cord blood stem cell-derived NK cells - Abstract
Down-regulation of HLA in tumor cells, low numbers and dysfunctionality of NK cells are commonly observed in patients with end-stage cervical cancer. Adoptive transfer of high numbers of cytotoxic NK cells might be a promising treatment approach in this setting. Here, we explored the cytotoxic efficacy on ten cervical cancer cell lines of activated allogeneic NK cells from two sources, i.e., peripheral blood (PBNK) with and without cetuximab (CET), a tumor-specific monoclonal antibody directed against EGFR, or derived from umbilical cord blood (UCB-NK). Whereas CET monotherapy was ineffective against the panel of cervical cancer cell lines, irrespective of their EGFR expression levels and despite their RAS wt status, it significantly enhanced the in vitro cytotoxic efficacy of activated PBNK (P = 0.002). Equally superior cytotoxicity over activated PBNK alone was achieved by UCB-NK (P
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