Journal
JOURNAL OF CLINICAL ONCOLOGY
Volume 27, Issue 6, Pages 945-952Publisher
AMER SOC CLINICAL ONCOLOGY
DOI: 10.1200/JCO.2008.18.0794
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Funding
- Fund for the Promotion of Scientific and Technological Development [FONDEF DO2I1088]
- National Fund for Scientific and Technological Development [FONDECYT 1060935, 1070559]
- Millennium Nucleus on Immunology and Immunotherapy [P04/030-F]
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Purpose The aim of this work was to assess immunologic response, disease progression, and post-treatment survival of melanoma patients vaccinated with autologous dendritic cells (DCs) pulsed with a novel allogeneic cell lysate (TRIMEL) derived from three melanoma cell lines. Patients and Methods Forty-three stage IV and seven stage III patients were vaccinated four times with TRIMEL/DC vaccine. Specific delayed type IV hypersensitivity (DTH) reaction, ex vivo cytokine production, and regulatory T-cell populations were determined. Overall survival and disease progression rates were analyzed using Kaplan-Meier curves and compared with historical records. Results The overall survival for stage IV patients was 15 months. More than 60% of patients showed DTH-positive reaction against the TRIMEL. Stage IV/DTH-positive patients displayed a median survival of 33 months compared with 11 months observed for DTH-negative patients (P = .0014). All stage III treated patients were DTH positive and remained alive and tumor free for a median follow-up period of 48 months (range, 33 to 64 months). DTH-positive patients showed a marked reduction in the proportion of CD4+ transforming growth factor (TGF) beta+ regulatory T cells compared to DTH-negative patients (1.54% v 5.78%; P < .0001). Conclusion Our findings strongly suggest that TRIMEL-pulsed DCs provide a standardized and widely applicable source of melanoma antigens, very effective in evoking antimelanoma immune response. To our knowledge, this is the first report describing a correlation between vaccine-induced reduction of CD4+TGF beta+ regulatory T cells and in vivo antimelanoma immune response associated to improved patient survival and disease stability.
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