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Dendritic Cells Engineered to Express Defined Allo‐HLA Peptide Complexes Induce Antigen‐specific Cytotoxic T Cells Efficiently Killing Tumour Cells

Dendritic Cells Engineered to Express Defined Allo‐HLA Peptide Complexes Induce Antigen‐specific... Most tumour‐associated antigens (TAA) are non‐mutated self‐antigens. The peripheral T cell repertoire is devoid of high‐avidity TAA‐specific cytotoxic T lymphocytes (CTL) due to self‐tolerance. As tolerance is major histocompatibility complex‐restricted, T cells may be immunized against TAA presented by a non‐self human leucocyte antigen (HLA) molecule and transferred to cancer patients expressing that HLA molecule. Obtaining allo‐restricted CTL of high‐avidity and low cross‐reactivity has, however, proven difficult. Here, we show that dendritic cells transfected with mRNA encoding HLA‐A*0201, efficiently present externally loaded peptides from the antigen, Melan‐A/MART‐1 to T cells from HLA‐A*0201‐negative donors. CD8+ T cells binding HLA‐A*0201/MART‐1 pentamers were detected already after 12 days of co‐culture in 11/11 donors. The majority of cells from pentamer+ cell lines were CTL and efficiently killed HLA‐A*0201+ melanoma cells, whilst sparing HLA‐A*0201+ B‐cells. Allo‐restricted CTL specific for peptides from the leukaemia‐associated antigens CD33 and CD19 were obtained with comparable efficiency. Collectively, the results show that dendritic cells engineered to express defined allo‐HLA peptide complexes are highly efficient in generating CTL specifically reacting with tumour‐associated antigens. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Scandinavian Journal of Immunology Wiley

Dendritic Cells Engineered to Express Defined Allo‐HLA Peptide Complexes Induce Antigen‐specific Cytotoxic T Cells Efficiently Killing Tumour Cells

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References (36)

Publisher
Wiley
Copyright
Copyright © 2009 Wiley Subscription Services
ISSN
0300-9475
eISSN
1365-3083
DOI
10.1111/j.1365-3083.2008.02223.x
pmid
19284496
Publisher site
See Article on Publisher Site

Abstract

Most tumour‐associated antigens (TAA) are non‐mutated self‐antigens. The peripheral T cell repertoire is devoid of high‐avidity TAA‐specific cytotoxic T lymphocytes (CTL) due to self‐tolerance. As tolerance is major histocompatibility complex‐restricted, T cells may be immunized against TAA presented by a non‐self human leucocyte antigen (HLA) molecule and transferred to cancer patients expressing that HLA molecule. Obtaining allo‐restricted CTL of high‐avidity and low cross‐reactivity has, however, proven difficult. Here, we show that dendritic cells transfected with mRNA encoding HLA‐A*0201, efficiently present externally loaded peptides from the antigen, Melan‐A/MART‐1 to T cells from HLA‐A*0201‐negative donors. CD8+ T cells binding HLA‐A*0201/MART‐1 pentamers were detected already after 12 days of co‐culture in 11/11 donors. The majority of cells from pentamer+ cell lines were CTL and efficiently killed HLA‐A*0201+ melanoma cells, whilst sparing HLA‐A*0201+ B‐cells. Allo‐restricted CTL specific for peptides from the leukaemia‐associated antigens CD33 and CD19 were obtained with comparable efficiency. Collectively, the results show that dendritic cells engineered to express defined allo‐HLA peptide complexes are highly efficient in generating CTL specifically reacting with tumour‐associated antigens.

Journal

Scandinavian Journal of Immunology – Wiley

Published: Jan 1, 2009

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