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.