Login
- Titel:
Toll-like receptor 7/8-matured RNA-transduced dendritic cells as post-remission therapy in acute myeloid leukaemia: results of a phase I trial.
- Dokumenttyp:
- Journal Article
- Autor(en):
- Lichtenegger, Felix S; Schnorfeil, Frauke M; Rothe, Maurine; Deiser, Katrin; Altmann, Torben; Bücklein, Veit L; Köhnke, Thomas; Augsberger, Christian; Konstandin, Nikola P; Spiekermann, Karsten; Moosmann, Andreas; Boehm, Stephan; Boxberg, Melanie; Heemskerk, Mirjam Hm; Goerlich, Dennis; Wittmann, Georg; Wagner, Beate; Hiddemann, Wolfgang; Schendel, Dolores J; Kvalheim, Gunnar; Bigalke, Iris; Subklewe, Marion
- Abstract:
- 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 10× 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 <65 and in patients mounting an immune response. Our observations need to be validated in a larger patient cohort. We hypothesise that TLR7/8 DC vaccination strategies should be combined with hypomethylating agents or checkpoint inhibition to augment immune responses. Trial registration: The study was registered at https://clinicaltrials.gov on 17 October 2012 (NCT01734304) and at https://www.clinicaltrialsregister.eu (EudraCT-Number 2010-022446-24) on 10 October 2013.
- Zeitschriftentitel:
- Clin Transl Immunology
- Jahr:
- 2020
- Band / Volume:
- 9
- Heft / Issue:
- 3
- Volltext / DOI:
- doi:10.1002/cti2.1117
- PubMed:
- http://view.ncbi.nlm.nih.gov/pubmed/32153780
- TUM Einrichtung:
- Institut für Allgemeine Pathologie und Pathologische Anatomie
BibTeX