K-ras突变多肽与全细胞抗原致敏DCs诱导CTLs对胰腺癌的杀伤活性研究(英文)

来源 :Chinese-German Journal of Clinical Oncology | 被引量 : 0次 | 上传用户:xuxuwanju
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Objective:We studied the role of specific cytotoxic T lymphocytes (CTLs) activated by dendritic cells (DCs) presenting cationic nanoparticles with the K-ras (12-Val) mutant peptide and whole tumor antigen in the killing of different pancreatic cancer cell lines in vitro and in vitro.Methods:Peripheral blood DCs were induced by rhGM-CSF and IL-4 and cultured.DCs were sensitized by whole antigen of a pancreatic cancer cell line (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 3 H-TdR test,and ELISA was performed to detect IFN-γ secretion.125 I-UdR was used to measure the killing effect of CTLs.We also evaluated the antitumor activity of CTLs in vivo in a tumor-bearing nude mouse model prepared with the PANC-1 (K-ras+) and SW1990 (K-ras-) cell lines.Results:Compared with K-ras+peptide,low concentration K-ras+peptide-CNP can be effectively presented by DCs (P < 0.05).CTLs induced by DCs pulsed with whole tumor antigen had significant 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) for PANC-1 and no effect (P > 0.05) on SW1990 cell lines (P > 0.05).Conclusion:Cationic nanoparticles with K-ras (12-Val) mutant peptide can be effectively presented by DCs at a low concentration in a short time.CTLs induced by K-ras+peptide-CNP had specific killing activity for the pancreatic cancer cell line with the K-ras (12-Val) mutant and could significantly inhibit tumor growth and increase the survival time of tumor-bearing nude mice. Objective: We studied the role of specific cytotoxic T lymphocytes (CTLs) activated by dendritic cells (DCs) vitro and peripheral in vitro.Methods: Peripheral blood DCs were induced by rhGM-CSF and IL-4 and cultured. DCs were sensitized by whole antigen of a pancreatic cancer cell line (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 3 H-TdR test, and ELISA was performed to detect IFN-γ secretion. 125 I-UdR was used to measure the killing effect of CTLs. We also evaluate the antitumor activity of CTLs in vivo in a tumor-bearing nude mouse model prepared with the PANC- 1 (K-ras +) and SW1990 (K-ras-) cell lines. Results: Compared with K-ras + p (P <0.05) on PANC-1 and SW1990 pancreatic cancer (P <0.05). CTLs induced by DCs pulsed with whole tumor antigen had significant greater killing effect 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) Conclusions: Cationic nanoparticles with K-ras (12-Val) mutant peptide can be effectively presented by DCs at a low concentration in a short time (P> 0.05) on SW1990 cell lines CTLs induced by K-ras + peptide-CNP had specific killing activity for the pancreatic cancer cell line with the K-ras (12-Val) mutant and could significantly inhibit tumor growth and increase the survival time of tumor-bearing nude mice.
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