Format

Send to

Choose Destination
Clin Cancer Res. 2012 Oct 1;18(19):5460-70. doi: 10.1158/1078-0432.CCR-11-3368. Epub 2012 Aug 15.

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 information

1
Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands.

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 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.

PMID:
22896657
DOI:
10.1158/1078-0432.CCR-11-3368
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center