Midostaurin abrogates CD33-directed UniCAR and CD33-CD3 bispecific antibody therapy in acute myeloid leukaemia

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

Combinatory therapeutic approaches of different targeted therapies in acute myeloid leukaemia are currently under preclinical/early clinical investigation. To enhance anti-tumour effects, we combined the tyrosine kinase inhibitor (TKI) midostaurin and T-cell mediated immunotherapy directed against CD33. Clinically relevant concentrations of midostaurin abrogated T-cell mediated cytotoxicity both after activation with bispecific antibodies and chimeric antigen receptor T cells. This information is of relevance for clinicians exploring T-cell mediated immunotherapy in early clinical trials. Given the profound inhibition of T-cell functionality and anti-tumour activity, we recommend specific FLT3 TKIs for further clinical testing of combinatory approaches with T-cell based immunotherapy.

Details

Original languageEnglish
Pages (from-to)735-740
Number of pages6
JournalBritish journal of haematology
Volume186
Issue number5
Publication statusPublished - 2019
Peer-reviewedYes

External IDs

PubMed 31119728

Keywords

ASJC Scopus subject areas

Keywords

  • acute myeloid leukaemia, combinatory therapy, midostaurin, T-cell based immunotherapy