title: Tandem therapy for retinoblastoma: immunotherapy and chemotherapy enhance cytotoxicity on retinoblastoma by increasing apoptosis.
abstract: OBJECTIVE
  The goal of this study was to provide an experimental basis for the clinical application of cell immunotherapy on RB in combination with chemotherapy treatment and to explore the mechanism of their combined cytotoxicity.
  
  
  METHODS
  We investigated the antitumor effect of cytokine-induced killer cells (CIK), co-cultivated with dendritic cells pulsed with tumor antigens (DC-Ag) and/or with carboplatin. Cytotoxicity was evaluated on a retinoblastoma cell line (RB-Y79) by FCM and immunofluorescence microscopy. Time-lapse video microscopy was used to follow the sequence of events during the carboplatin and CIK cytotoxicity.
  
  
  RESULTS
  Our results showed that a small proportion of RB-Y79 cells died after a low-dose carboplatin application. The cell population recovered 5 days after carboplatin was removed from the culture medium. Three times fewer normal epithelium retina cell lines (hTERT-RPE1) died at the same carboplatin dose. CIK achieved 5 times more cytotoxicity against RB cells pre-treated with low dose of carboplatin, showing the highest antitumor activity in the tandem carboplatin-DC-Ag-CIK-carboplatin treatment. Time-lapse video microscopy revealed that carboplatin-preconditioned RB cells are more avidly engaged by CIK cells, increasing RB mortality and resulting in an overall increment in apoptosis.
  
  
  CONCLUSIONS
  This study provides evidence that carboplatin combined with cell immunotherapy is superior to carboplatin alone to kill RB cells in vitro. We propose that a primary application of a low dose of a chemotherapeutic drug that is able to attack the tumor, and a subsequent treatment with highly effective immunotherapy based on DC-Ag-CIK cells could be a safe and selective treatment for RB.
authors.affiliation: Department of Pediatrics, The General Hospital of the Chinese People's Armed Police Forces, Beijing 100039, China.
authors.forename: Qiuling
authors.initials: Q
authors.lastname: Liu
authors.forename: Yafeng
authors.initials: Y
authors.lastname: Wang
authors.forename: Han
authors.initials: H
authors.lastname: Wang
authors.forename: Yingying
authors.initials: Y
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Patricia Elena
authors.initials: PE
authors.lastname: Kunda
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D016190:Carboplatin / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D055612:Cytokine-Induced Killer Cells / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008856:Microscopy, Fluorescence; D012175:Retinoblastoma
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D016190:Carboplatin