Umbilical Cord Blood-Derived Natural Killer Cells Combined with Bevacizumab for Colorectal Cancer Treatment.
Colorectal cancer (CRC) is among the cancers with the highest incidence globally, and it currently ranks as the fourth leading cause of cancer-related deaths worldwide. Novel strategies for the treatment of advanced CRC are urgently needed, and adoptive transfer of allogeneic natural killer (NK) cells represents an attractive option. In this study, we successfully expanded NK cells from umbilical cord blood (UCB) with membrane-bound interleukin (IL)-21, termed eUCB-NK cells. eUCB-NK cells efficiently lysed CRC cell lines in vitro and secreted significantly higher levels of interferon-γ, tumor necrosis factor-α, granulocyte-macrophage colony stimulating factor, and chemokine ligand 3 compared with IL-2-stimulated NK cells. Adoptive transfer of these NK cells significantly inhibited the growth of HT29 xenografts, whereas LoVo tumors were not effectively controlled with eUCB-NK cells. Higher numbers of NK cells inside HT29 tumors, not seen in LoVo tumors, might contribute to the differences in response to eUCB-NK cells. Bevacizumab increased extravasation of adoptively transferred NK cells into LoVo tumors and improved the therapeutic activity of eUCB-NK cells. These results justify clinical translation of UCB-derived NK cell-based therapeutics, used alone or in combination with bevacizumab, as a novel treatment option for patients with CRC.
['Xu|Chen|C|', 'Liu|Dongning|D|', 'Chen|Zhixin|Z|', 'Zhuo|Fan|F|', 'Sun|Huankui|H|', 'Hu|Jiaping|J|', 'Li|Taiyuan|T|']
D019264:Adoptive Transfer D000818:Animals D000920:Antibody-Dependent Cell Cytotoxicity D000074322:Antineoplastic Agents, Immunological D000068258:Bevacizumab D015415:Biomarkers D045744:Cell Line, Tumor D015179:Colorectal Neoplasms D003131:Combined Modality Therapy D003602:Cytotoxicity, Immunologic D004195:Disease Models, Animal D005312:Fetal Blood D006801:Humans D016130:Immunophenotyping D007694:Killer Cells, Natural D051379:Mice D009389:Neovascularization, Pathologic D023041:Xenograft Model Antitumor Assays
natural killer cell bevacizumab colorectal cancer umbilical cord blood