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Monographic Report
Specific CTL response induced by dendritic cells pulsed with HER-2/neu peptide
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Abstract:
Objective : To explore the potential of autologous dendritic cells (DCs) pulsed with HER-2/neu peptide in inducing specific cytotoxic T lymphocyte (CTL) response and feasibility of breast cancer vaccines. Methods: Seventeen breast cancer patients with positive HLA-A201 and HER-2/neu were enrolled and their peripheral blood mononuclear cells and lymphocytes were isolated and induced into DCs and pulsed with HER-2/neu peptide. The killing effect of CTLs against T2 cell line pulsed with HLA-A201-binding peptide HER-2/neu was determined. The patients were inoculated subcutaneously near the inguinal region with auto-DCs pulsed with HER-2/neu peptide for 4 times every week. The immunological responses and clinical responses were examined in 1 week after the final vaccination. Results: The average percentage of special CTLs primed by DCs pulsed with HER-2/neu peptide was significantly higher than that in the control group (CTLs primed by DCs unloaded with HER-2/neu peptide) （\[5.41±1.44\]% vs \[0.41±0.12\]%, P<0.05). CTLs induced by DCs exerted a stronger killing effect on T2 cell line pulsed with HER-2/neu peptide than that in control group （\[35.5±4.7\]% vs \[11.2±1.4\]% at the ratio of E \[effect\] to T \[target\] as 30 ∶1，P<0.05). Vaccination of DCs was well tolerated and no toxicity was observed. The cytokine levels in sera such as IL-2, IL-12 and IFN-γ were increased after vaccinations （\[148.79±28.32\] ng/ml vs \[409.09±89.39\] ng/ml,\[24.49±56.23\] ng/ml vs \[56.23±14.08\] ng/ml, \[67.77±39.35\] ng/ml vs \[146.57±25.97\] ng/ml, respectively, all P<0.05). The cytokine levels in sera such as TNF-α and IL-10 had no significant changes before and after vaccination. The results of DTH test were positive in 8 patients (8/17), and the percentages of antigen-specific IFN-γ + CD8 +T increased in 8 patients (8/17). Conclusion: Auto-DC vaccines pulsed with HER-2/neu peptide can elicit specific immune responses ex vivo and in vivo, and induce secretion of Th1 type cytokines from DCs and have no adverse reaction.
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Project Supported:
Project supported by the High Technology Industrialization Project from Nanjing Science and Technology Commission（No.201103058）
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