Title: | Vaccination with mRNA-Electroporated Dendritic Cells Induces Robust Tumor Antigen-Specific CD4+ and CD8+ T Cells Responses in Stage III and IV Melanoma Patients |
Author(s): | Aarntzen, E.H.J.G. ; Schreibelt, G. ; Bol, K.F. ; Lesterhuis, W.J. ; Croockewit, A.J. ; Wilt, J.H. de ; Rossum, M.M. van ; Blokx, W.A.M. ; Jacobs, J.F.M. ; Duiveman-de Boer, T. ; Schuurhuis, D.H.; Mus, R.D. ; Thielemans, K.; Vries, I.J.M. de ; Figdor, C.G. ; Punt, C.J.A. ; Adema, G.J. |
Publication year: | 2012 |
Source: | Clinical Cancer Research, vol. 18, iss. 19, (2012), pp. 5460-5470 |
ISSN: | 1078-0432 |
DOI: | https://doi.org/10.1158/1078-0432.CCR-11-3368 |
Publication type: | Article / Letter to editor |
Please use this identifier to cite or link to this item : https://hdl.handle.net/2066/110140 ![]() |
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Subject: | N4i 2: Invasive mycoses and compromised host ONCOL 3: Translational research N4i 4: Auto-immunity, transplantation and immunotherapy NCMLS 2: Immune Regulation N4i 4: Auto-immunity, transplantation and immunotherapy ONCOL 1: Hereditary cancer and cancer-related syndromes NCMLS 2: Immune Regulation ONCOL 3: Translational research ONCOL 2: Age-related aspects of cancer ONCOL 3: Translational research NCMLS 2: Immune Regulation ONCOL 4: Quality of Care ONCOL 5: Aetiology, screening and detection |
Organization: | Nuclear Medicine Tumorimmunology Medical Oncology Haematology Surgery Dermatology Pathology Laboratory of Medical Immunology Paediatrics - OUD tm 2017 Radiology |
Journal title: |
Clinical Cancer Research
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Volume: | vol. 18 |
Issue: | iss. 19 |
Page start: | p. 5460 |
Page end: | p. 5470 |
Abstract: |
PURPOSE: Electroporation of dendritic cells (DC) with mRNA encoding tumor-associated antigens (TAA) has multiple advantages compared to peptide loading. We investigated the immunologic and clinical responses to vaccination with mRNA-electroporated DC in stage III and IV melanoma patients. Experimental design: Twenty-six stage III HLA*02:01 melanoma patients scheduled for radical lymph node dissection (stage III) and 19 melanoma patients with irresectable locoregional or distant metastatic disease (referred to as stage IV) were included. Monocyte-derived DC, electroporated with mRNA encoding gp100 and tyrosinase, were pulsed with keyhole limpet hemocyanin and administered intranodally. TAA-specific T-cell responses were monitored in blood and skin-test infiltrating lymphocyte (SKIL) cultures. RESULTS: Comparable numbers of vaccine-induced CD8(+) and/or CD4(+) TAA-specific T-cell responses were detected in SKIL cultures; 17/26 stage III patients and 11/19 stage IV patients. Strikingly, in this population, TAA-specific CD8(+) T cells that recognize multiple epitopes and produce elevated levels of IFNgamma upon antigenic challenge in vitro, were significantly more often observed in stage III patients; 15/17 versus 3/11 stage IV patients, P = 0.0033. In stage IV patients, one mixed and one partial response were documented. The presence or absence of IFNgamma-producing TAA-specific CD8(+) T cells in stage IV patients was associated with marked difference in median overall survival of 24.1 months versus 11.0 months, respectively. CONCLUSION: Vaccination with mRNA-electroporated DC induces a broad repertoire of IFNgamma producing TAA-specific CD8(+) and CD4(+) T-cell responses, particularly in stage III melanoma patients. Clin Cancer Res; 18(19); 5460-70. (c)2012 AACR.
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