학술논문
Toll‐like receptor 7/8‐matured RNA‐transduced dendritic cells as post‐remission therapy in acute myeloid leukaemia: results of a phase I trial
Document Type
article
Author
Felix S Lichtenegger; Frauke M Schnorfeil; Maurine Rothe; Katrin Deiser; Torben Altmann; Veit L Bücklein; Thomas Köhnke; Christian Augsberger; Nikola P Konstandin; Karsten Spiekermann; Andreas Moosmann; Stephan Boehm; Melanie Boxberg; Mirjam HM Heemskerk; Dennis Goerlich; Georg Wittmann; Beate Wagner; Wolfgang Hiddemann; Dolores J Schendel; Gunnar Kvalheim; Iris Bigalke; Marion Subklewe
Source
Clinical & Translational Immunology, Vol 9, Iss 3, Pp n/a-n/a (2020)
Subject
Language
English
ISSN
2050-0068
Abstract
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