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

Clinical & Translational Immunology
Felix S LichteneggerMarion Subklewe

Abstract

Innovative post-remission therapies are needed to eliminate residual AML cells. DC vaccination is a promising strategy to induce anti-leukaemic immune responses. 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. 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. Administration of TLR7/8-matured DCs to AML patients in CR at high risk of relapse was feasible and safe and resulte...Continue Reading

Associated Clinical Trials

Nov 27, 2012·PD Dr. Marion Subklewe

References

Mar 26, 2009·Journal of the National Cancer Institute·Nadia HowladerBrenda K Edwards
Jun 1, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Stefani SprangerBernhard Frankenberger
Jul 16, 2010·Proceedings of the National Academy of Sciences of the United States of America·Viggo F Van TendelooZwi N Berneman
Jul 21, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Avital L AmirMirjam H M Heemskerk
Sep 8, 2011·American Journal of Hematology·Djordje AtanackovicNicolaus Kröger
Mar 1, 2012·Journal of Translational Medicine·Stefani SprangerDolores J Schendel
Dec 22, 2012·Immunotherapy·Felix S LichteneggerMarion Subklewe
Mar 29, 2014·Nature Protocols·Matthias Wölfl, Philip D Greenberg
Sep 5, 2014·Cancer Immunology, Immunotherapy : CII·Marion SubkleweIris Bigalke
Sep 17, 2016·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Nirali N ShahTerry J Fry
May 10, 2017·Molecular Therapy. Methods & Clinical Development·Matthew WeinstockDavid Avigan
Jul 1, 2017·Hematology/oncology and Stem Cell Therapy·Adetola A Kassim, Bipib N Savani
Jul 27, 2017·Journal of Hematology & Oncology·Felix S LichteneggerMarion Subklewe
Sep 28, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Elizabeth A GriffithsMichael J Nemeth
Jan 10, 2018·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal
Mar 15, 2018·Frontiers in Immunology·Felix S LichteneggerMarion Subklewe
Mar 31, 2018·Frontiers in Immunology·Maarten VerstevenEva Lion

❮ Previous
Next ❯

Citations

Jan 13, 2021·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Joseph C RimandoJohn F DiPersio
Mar 28, 2021·Vaccine·Sara Sousa RosaMarco P C Marques
Jun 8, 2021·Molecular Therapy. Methods & Clinical Development·Julia K Bialek-WaldmannRenata Stripecke

❮ Previous
Next ❯

Methods Mentioned

BETA
leukapheresis
flow cytometry
biopsies
FACS
CLIP

Software Mentioned

FlowJo

Related Concepts

Related Feeds

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.

AML: Role of LSD1 by CRISPR (Keystone)

Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.

Acute Myeloid Leukaemia & RNA

Acute myeloid leukaemia (AML) is a common hematological type of cancer. As the population ages, there has been a rise in the frequency of AML. RNA expression has been used to see if there are different genetic profiles that exist within AML and whether these may underpin the variations in survival rates. Here is the latest research on AML and RNA.