Antitumor efficacy of specific cytotoxic T lymphocytes activiated by dendritic cells pulsed with K-ras antigen to pancreatic cancer ex vivo
- VernacularTitle:负载K-ras抗原的DCs诱导CTLs对胰腺癌的体外杀伤作用
- Author:
Li XU
;
Yanqiu FANG
;
Guang TAN
;
Zhongyu WANG
;
Yan TAN
- Publication Type:Journal Article
- Keywords:
Pancreatic cancer;
Dendritic cells;
K-ras peptide
- From:
Chinese Journal of Immunology
2009;25(12):1075-1079,1091
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the antitumor efficiency of the special cytotoxic T lymphocytes(CTLs) activated by dendritic cells(DCs) pulsed with K-ras (12-Val) antigen.Methods:DCs was generated from PBMC in the presence of granuloceyte/macrophage-colony stimulating factor(GM-CSF),interleukin-4(IL-4)in vitro.DCs were differently sensitized with K-ras mutant pancreatic cancer cell line,K-ras(12-Val) mutant peptide,K-ras(12-Val) mutant peptide with the surface of cationic nanoparticle.Cell surface markers on DCs was measured by flow cytometry.The activation of CTL induced by DCs was detected by ~3H- thymidine incorporation test.The killing effects of CTL to pancreatic cancer was detected by ~(125)I-UdR release test. Production of IL-12 and IFN-γ by DCs and PBMC was detected by ELISA.Results:Compared with DCs pulsed with K-ras(12-Val) mutant peptide and K-ras (12-Val) mutant peptide with the surface of cationic nanoparticle,DCs pulsed with whole tumor antigen could better induce CTLs killing activity(P＜0.05).The DCs with K-ras(12-Val) mutant peptide and K-ras mutant peptide with the surface of cationic nanoparticle could produce specific CTL killing activity aganist pancreatic cancer cell line Patu8988(K-ras+)(P＜0.05),but not SW1990(K-ras-)(P＞0.05). K-ras (12-Val) mutant peptide with the surface of cationic nanoparticle at lower concentrations can be effectively presenting on the surface of DCs than only K-ras (12-Val) mutant peptide.Conclusion:K-ras (12-Val) mutant peptide with cationic carrier can be effectively presenting and expression of DCs and induce CTL specific killing activity aganist pancreatic cancer cell lines with K-ras (12-Val) mutant peptide.
