Induction of CTLs by DCs pulsed with K-ras mutant peptide on the surface of nanoparticles in the treatment of pancreatic cancer

  • Authors:
    • Guang Tan
    • Zhongyu Wang
    • Xin Zhang
    • Zhengang Cai
    • Junkai Zhang
  • View Affiliations

  • Published online on: April 28, 2011     https://doi.org/10.3892/or.2011.1283
  • Pages: 215-221
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Abstract

The aim of this study was to investigate the role of specific cytotoxic T lymphocytes (CTLs) activated by dendritic cells (DCs) presenting cationic nanoparticles with the K-ras (12-Val) mutant peptide in the killing of different pancreatic cancer cell lines in vivo and in vitro. Peripheral blood DCs were induced by rhGM-CSF and IL-4 and cultured. DCs were sensitized by whole antigen of PANC-1 with expression of K-ras mutant, K-ras mutant peptide (K-ras+peptide) and cationic nanoparticles with K-ras mutant peptide (K-ras+peptide-CNP), respectively. Cell surface markers were measured by flow cytometry. Lymphocyte proliferation was detected by the 3H-TdR test, and IL-12 and IFN‑γ secretion was detected by ELISA. 125I-UdR was used to measure the killing effect of CTLs. The antitumor activity of CTLs in tumor-bearing nude mouse models prepared with PANC-1 and SW1990 cells was evaluated. Results showed that, compared with K-ras+peptide, low concentrations of K-ras+peptide-CNP were effectively presented by DCs (P<0.05). CTLs induced by DCs pulsed with whole tumor antigen had a significantly greater killing effect (P<0.05) on PANC-1 and SW1990 pancreatic cancer cells compared with K-ras+peptide- and K-ras+peptide-CNP-induced CTLs. CTLs induced by DCs pulsed with K-ras+peptide and K-ras+peptide- CNP had a specific killing effect (P<0.05) on PANC-1 cells and no effect (P>0.05) on SW1990 cells. In conclusion, cationic nanoparticles with the K-ras (12-Val) mutant peptide can be effectively presented by DCs at a low concentration. CTLs induced by K-ras+peptide-CNP had specific killing activity for the pancreatic cancer cell line with the K-ras mutant and significantly inhibited tumor growth and increased the survival time of tumor-bearing nude mice. Although this study confirmed that whole cell antigen induced a good antitumor immune response, the possibility of immune tolerance and autoimmunity which has been previously proven contribute to the difficulty in the application of this DC vaccine.

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July 2011
Volume 26 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Tan G, Wang Z, Zhang X, Cai Z and Zhang J: Induction of CTLs by DCs pulsed with K-ras mutant peptide on the surface of nanoparticles in the treatment of pancreatic cancer. Oncol Rep 26: 215-221, 2011
APA
Tan, G., Wang, Z., Zhang, X., Cai, Z., & Zhang, J. (2011). Induction of CTLs by DCs pulsed with K-ras mutant peptide on the surface of nanoparticles in the treatment of pancreatic cancer. Oncology Reports, 26, 215-221. https://doi.org/10.3892/or.2011.1283
MLA
Tan, G., Wang, Z., Zhang, X., Cai, Z., Zhang, J."Induction of CTLs by DCs pulsed with K-ras mutant peptide on the surface of nanoparticles in the treatment of pancreatic cancer". Oncology Reports 26.1 (2011): 215-221.
Chicago
Tan, G., Wang, Z., Zhang, X., Cai, Z., Zhang, J."Induction of CTLs by DCs pulsed with K-ras mutant peptide on the surface of nanoparticles in the treatment of pancreatic cancer". Oncology Reports 26, no. 1 (2011): 215-221. https://doi.org/10.3892/or.2011.1283