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Lichtenegger, F.S.* ; Schnorfeil, F.M.* ; Rothe, M.* ; Deiser, K.* ; Altmann, T.* ; Bücklein, V.L.* ; Köhnke, T.* ; Augsberger, C.* ; Konstandin, N.P.* ; Spiekermann, K.* ; Moosmann, A. ; Boehm, S.* ; Boxberg, M.* ; Heemskerk, M.H.M.* ; Goerlich, D.* ; Wittmann, G.* ; Wagner, B.* ; Hiddemann, W.* ; Schendel, D.J.* ; Kvalheim, G.* ; Bigalke, I.* ; Subklewe, M.*

Toll-like receptor 7/8-matured RNA-transduced dendritic cells as post-remission therapy in acute myeloid leukaemia: Results of a phase I trial.

Clin. Transl. Immunology 9:e1117 (2020)
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Objectives Innovative post-remission therapies are needed to eliminate residual AML cells. DC vaccination is a promising strategy to induce anti-leukaemic immune responses.Methods We conducted a first-in-human phase I study using TLR7/8-matured DCs transfected with RNA encoding the two AML-associated antigens WT1 and PRAME as well as CMVpp65. AML patients in CR at high risk of relapse were vaccinated 10x over 26 weeks.Results Despite heavy pretreatment, DCs of sufficient number and quality were generated from a single leukapheresis in 11/12 cases, and 10 patients were vaccinated. Administration was safe and resulted in local inflammatory responses with dense T-cell infiltration. In peripheral blood, increased antigen-specific CD8(+) T cells were seen for WT1 (2/10), PRAME (4/10) and CMVpp65 (9/10). For CMVpp65, increased CD4(+) T cells were detected in 4/7 patients, and an antibody response was induced in 3/7 initially seronegative patients. Median OS was not reached after 1057 days; median RFS was 1084 days. A positive correlation was observed between clinical benefit and younger age as well as mounting of antigen-specific immune responses.Conclusions Administration of TLR7/8-matured DCs to AML patients in CR at high risk of relapse was feasible and safe and resulted in induction of antigen-specific immune responses. Clinical benefit appeared to occur more likely in patients The study was registered at on 17 October 2012 (NCT01734304) and at (EudraCT-Number 2010-022446-24) on 10 October 2013.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Acute Myeloid Leukaemia ; Cancer Vaccines ; Clinical Trials ; Dendritic Cell Vaccination ; Immunotherapy; Testis Antigen-expression; T-lymphocyte Responses; Immunotherapy; Vaccination; Induction; Generation
Language english
Publication Year 2020
HGF-reported in Year 2020
ISSN (print) / ISBN 2050-0068
e-ISSN 2050-0068
Journal Clinical and translational immunology
Quellenangaben Volume: 9, Issue: 3, Pages: , Article Number: e1117 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Research Unit Gene Vector (AGV)
POF-Topic(s) 30203 - Molecular Targets and Therapies
Research field(s) Immune Response and Infection
PSP Element(s) G-501500-001
DOI 10.1002/cti2.1117
WOS ID WOS:000522447300007
Scopus ID 85082424877
PubMed ID 32153780
Erfassungsdatum 2020-04-20
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