Characterization of CD8+T-Cell Responses in the Peripheral Blood and Skin Injection Sites of Melanoma Patients Treated with mRNA Electroporated Autologous Dendritic Cells (TriMixDC-MEL)

Daphné Benteyn,Jurgen Corthals,Kris Thielemans,Carlo Heirman,Sofie Wilgenhof,Aude Bonehill,An M T Van Nuffel,Bart Neyns

doi:10.1155/2013/976383

Abstract

Treatment of melanoma patients with mRNA electroporated dendritic cells (TriMixDC-MEL) stimulates T-cell responses against the presented tumor-associated antigens (TAAs). In the current clinical trials, melanoma patients with systemic metastases are treated, requiring priming and/or expansion of preexisting TAA-specific T cells that are able to migrate to both the skin and internal organs. We monitored the presence of TAA-specific CD8+ T cells infiltrating the skin at sites of intradermal TriMixDC-MEL injection (SKILs) and within the circulation of melanoma patients treated in two clinical trials. In 10 out of fourteen (71%) patients screened, CD8+ T cells recognizing any of the four TAA presented by TriMixDC-MEL cellular vaccine were found in both compartments. In total, 30 TAA-specific T-cell responses were detected among the SKILs and 29 among peripheral blood T cells, of which 24 in common. A detailed characterization of the antigen specificity of CD8+ T-cell populations in four patients indicates that the majority of the epitopes detected were only recognized by CD8+ T cells derived from either skin biopsies or peripheral blood, indicating that some compartmentalization occurs after TriMix-DC therapy. To conclude, functional TAA-specific CD8+ T cells distribute both to the skin and peripheral blood of patients after TriMixDC-MEL therapy.

Highlights

Several cancer immunotherapeutic approaches are currently under investigation, amongst which dendritic-cell-based immunotherapy
In the current clinical trials, melanoma patients with systemic metastases are treated, re uiring priming and/or expansion of preexisting tumor-associated antigens (TAAs)-speci c T cells that are able to migrate to both the skin and internal organs. e monitored the presence of TAA-speci c CD8+ T cells in ltrating the skin at sites of intradermal TriMixDCMEL injection (SKILs) and within the circulation of melanoma patients treated in two clinical trials
Immune monitoring of melanoma patients a er Dendritic cells (DCs) treatment was performed on skin biopsies and on peripheral blood

Summary

Introduction

Several cancer immunotherapeutic approaches are currently under investigation, amongst which dendritic-cell-based immunotherapy. Dendritic cells (DCs) are potent antigenpresenting cells that can be loaded with antigens. Recent improvements of DC therapy include the use of mRNA encoding full-length tumor antigen(s) instead of peptides to load DCs for clinical trials. Monitoring TAA-restricted T-cell responses during treatment is of great importance to investigate the immunogenicity of the vaccine and the potential correlation between the immune response and the clinical outcome of the patients and for future treatment design. Immune responses should be monitored within the tumor, but this site is not always accessible. Alternative methods are the characterization of circulating treatment-speci c CD8+ T cells in the peripheral blood [4,5,6], or the characterization of treatment-speci c skin in ltrating lymphocytes (SKILs) at delayed type hypersensitivity (DTH) sites [7, 8].

Methods

Results

Conclusion