Cytokine-induced killer (CIK) cells bound with anti-CD3/anti-CD133 bispecific antibodies target CD133high 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 CD133high cells produced significantly (p < 0.05) higher amount of IFN-gamma. Treatment with the BsAb CIK cells significantly downregulated the expression of S100P and IL-18 bp, 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. (C) 2013 Elsevier Inc. All rights reserved.