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Journal of Cancer Research and Clinical Oncology

, Volume 139, Issue 8, pp 1357–1372 | Cite as

Tandem therapy for retinoblastoma: immunotherapy and chemotherapy enhance cytotoxicity on retinoblastoma by increasing apoptosis

  • Qiuling Liu
  • Yafeng Wang
  • Han Wang
  • Yingying Liu
  • Tao Liu
  • Patricia Elena KundaEmail author
Original Paper

Abstract

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 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.

Conclusion

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.

Keywords

Retinoblastoma Carboplatin Dendritic cells Cytokine-induced killer cells Annexin V Apoptosis 

Notes

Acknowledgments

We are grateful to Dr. Cristian Acosta for insightful comments on the manuscript and English editing. We thank Poten Biomedical Company (Shenzhen, China) for providing technical support and Guillaume Charras for Life-ActGFP plasmid. This work was supported by both Shenzhen Development and Reform Commission (Grants number: [2011]1680) and the Capital Clinical Features Applied Research Plan (Grants number: Z121107001012055). P.K., Y.L, H.W and T.L are supported in part by Poten Biomedical Institute for Cancer Immunotherapy.

Conflict of interest

No potential conflicts of interest were disclosed.

Supplementary material

432_2013_1448_MOESM1_ESM.pdf (104 kb)
Supplementary material 1 (PDF 104 kb)

Supplementary material 2 (MPG 2098 kb)

Supplementary material 3 (MPG 2068 kb)

Supplementary material 4 (MPG 1424 kb)

432_2013_1448_MOESM5_ESM.doc (23 kb)
Supplementary material 5 (DOC 23 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Qiuling Liu
    • 1
  • Yafeng Wang
    • 1
    • 2
  • Han Wang
    • 3
  • Yingying Liu
    • 3
  • Tao Liu
    • 3
  • Patricia Elena Kunda
    • 3
    Email author
  1. 1.Department of PediatricsThe General Hospital of the Chinese People’s Armed Police ForcesBeijingChina
  2. 2.Graduate DivisionXinxiang Medical UniversityXinxiangChina
  3. 3.Poten Biomedical Institute for Cancer ImmunotherapyShenzhenChina

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