INICSA   23916
INSTITUTO DE INVESTIGACIONES EN CIENCIAS DE LA SALUD
Unidad Ejecutora - UE
artículos
Título:
Tandem therapy for retinoblastoma: Immunotherapy and chemotherapy enhance cytotoxicity on retinoblastoma by increasing apoptosis
Autor/es:
LIU Q, WANG Y, WANG H, LIU Y, LIU T, KUNDA PE
Revista:
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
Editorial:
SPRINGER
Referencias:
Lugar: Berlin; Año: 2013 p. 1357 - 1372
ISSN:
0171-5216
Resumen:
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.