| Autor: |
Gosse J. Adema, Cornelis J. A. Punt, Carl G. Figdor, I. Jolanda M. de Vries, Kris Thielemans, Roel Mus, Danita H. Schuurhuis, Tjitske Duiveman-de Boer, Joannes F. M. Jacobs, Willeke A. M. Blokx, Michelle M. van Rossum, Johannes H. W. de Wilt, Alexandra J. Croockewit, W. Joost Lesterhuis, Kalijn Bol, Gerty Schreibelt, Erik H. J. G. Aarntzen |
| Rok vydání: |
2023 |
| DOI: |
10.1158/1078-0432.c.6522750.v1 |
| Popis: |
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 IFNγ 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 IFNγ-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 IFNγ producing TAA-specific CD8+ and CD4+ T-cell responses, particularly in stage III melanoma patients. Clin Cancer Res; 18(19); 5460–70. ©2012 AACR. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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