INSTITUTO DE INVESTIGACIONES EN CIENCIAS DE LA SALUD
Unidad Ejecutora - UE
Tandem therapy for retinoblastoma: Immunotherapy and chemotherapy enhance cytotoxicity on retinoblastoma by increasing apoptosis
LIU Q, WANG Y, WANG H, LIU Y, LIU T, KUNDA PE
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
Lugar: Berlin; Año: 2013 p. 1357 - 1357
Purpose 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 cyto- kine-induced killer cells (CIK), co-cultivated with dendritic cells pulsed with tumor antigens (DC-Ag) and/or with carboplatin. Cytotoxicity was evaluated on a retinoblas- toma 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. Conclusion This study provides evidence that carboplatin combined with cell immunotherapy is superior to carbo- platin 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 treatmentfor RB.