title: Cytokine-induced killer (CIK) cells bound with anti-CD3/anti-CD133 bispecific antibodies target CD133(high) cancer stem cells in vitro and in vivo.
abstract: 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.
authors.affiliation: Department of Immunology, PLA General Hospital, Beijing, China. Electronic address: huangjh123@yahoo.com.cn.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Huang
authors.forename: Chonghui
authors.initials: C
authors.lastname: Li
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.forename: Haiyan
authors.initials: H
authors.lastname: Lv
authors.forename: Yelei
authors.initials: Y
authors.lastname: Guo
authors.forename: Hanren
authors.initials: H
authors.lastname: Dai
authors.forename: Max S
authors.initials: MS
authors.lastname: Wicha
authors.forename: Alfred E
authors.initials: AE
authors.lastname: Chang
authors.forename: Qiao
authors.initials: Q
authors.lastname: Li
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D018033:Antibodies, Bispecific / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity; D015703:Antigens, CD / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D045744:Cell Line, Tumor; D055612:Cytokine-Induced Killer Cells / Q000276:immunology*; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D014411:Neoplastic Stem Cells / Q000276:immunology; D010455:Peptides / Q000276:immunology*; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D000071916:AC133 Antigen; D018033:Antibodies, Bispecific; D015703:Antigens, CD; D017252:CD3 Complex; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D007371:Interferon-gamma
keywords: Bispecific antibody (BsAb);; CD133; CD3;; Cancer stem cell (CSC);; Cytokine induced killer (CIK) cells;