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Hammer, M.H.* ; Meyer, S.* ; Brestrich, G.* ; Moosmann, A. ; Kern, F.* ; Tesfa, L.* ; Babel, N.* ; Mittenzweig, A.* ; Rooney, C.M.* ; Hammerschmidt, W. ; Volk, H.-D.*

HLA type-independent generation of antigen-specific T cells for adoptive immunotherapy.

Eur. J. Immunol. 35, 2250-2258 (2005)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
Adoptive immunotherapy with antigen-specific T cells has been successfully used to treat certain infectious diseases and cancers. Although more patients may profit from T cell therapy, its more frequent use is restricted by limitations in current T cell generation strategies. The most commonly applied peptide-based approaches rely on the knowledge of relevant epitopes. Therefore, T cells cannot be generated for diseases with unknown epitopes or for patients with unfavorable HLA types. We developed a peptide-based approach for HLA type-independent generation of specific T cells against various proteins. It is based on short-time stimulation with peptide libraries that cover most CD4+ and CD8+ T cell epitopes of given proteins. The procedure requires no prior knowledge of epitopes because libraries are synthesized solely on the basis of the protein's amino acid sequence. Stimulation is followed by immunomagnetic selection of activated IFN-γ-secreting cells and nonspecific expansion. To evaluate the protocol, we generated autologous T cells specific for a well-characterized antigen, the human cytomegalovirus phosphoprotein 65 (pp65). Generated T cell lines consisted of pp65-specific CD4+ and CD8+ lymphocytes that displayed antigen-specific killing and proliferation. The protocol combines the biosafety of peptide-based approaches with HLA type independence and may help to advance adoptive immunotherapy in the future.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords adoptive immunotherapy; antigen-specific T cells; peptide libraries; generation procedure
ISSN (print) / ISBN 0014-2980
e-ISSN 1521-4141
Journal European Journal of Immunology
Quellenangaben Volume: 35, Issue: 7, Pages: 2250-2258 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Hoboken
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Gene Vector (AGV)