Cytokine-induced killer (CIK) cells bound with anti-CD3/anti-CD133 bispecific antibodies target CD133(high) cancer stem cells in vitro and in vivo.

CD133 is a common marker of cancer stem cells (CSCs). We generated an anti-CD3/anti-CD133 bispecific antibody (BsAb) and bound it to the cytokine-induced killer (CIK) cells as effector cells (BsAb-CIK) to target CD133(high) CSCs. The killing of CD133(high) pancreatic (SW1990) and hepatic (Hep3B) cancer cells by the BsAb-CIK cells was significantly (p<0.05) higher than the killing by the parental CIK or by CIK cells bound with anti-CD3 (CD3-CIK) without CD133 targeting. In nude mice, the BsAb-CIK cells inhibited CD133(high) tumor growth significantly (p<0.05) more than that by CIK or CD3-CIK cells, or by the BsAb alone. BsAb-CIK cells co-cultured with CD133(high) cells produced significantly (p<0.05) higher amount of IFN-γ. Treatment with the BsAb-CIK cells significantly downregulated the expression of S100P and IL-18bp, but upregulated STAT1. The findings may help with the development of novel immunotherapies for patients with cancer containing CD133(high) CSCs by selectively targeting this cell population.