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

Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, PR China.
Oncology Reports (Impact Factor: 2.3). 07/2011; 26(1):215-21. DOI: 10.3892/or.2011.1283
Source: PubMed


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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    • "TLR-3 agonist complexed with cationic liposome augments vaccine-elicited anti-tumor immunity by enhancing TLR3-IFN regulatory factor (IRF)3 signaling and type I IFN in DCs (Wang et al., 2012). In addition, DCs pulsed with tumor Ag-loaded cationic NPs has been successfully reported to induce a specific cytotoxic response against different pancreatic cancer cell lines in vivo and in vitro (Tan et al., 2011). Although different types of NP-based drug delivery systems such as polymer conjugations, micelles, and liposome are available, solid lipid nanoparticles (SLN) falls superior. "
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