FLT3-directed UniCAR T-cell therapy of acute myeloid leukaemia

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

Adaptor chimeric antigen receptor (CAR) T-cell therapy offers solutions for improved safety and antigen escape, which represent main obstacles for the clinical translation of CAR T-cell therapy in myeloid malignancies. The adaptor CAR T-cell platform ‘UniCAR’ is currently under early clinical investigation. Recently, the first proof of concept of a well-tolerated, rapidly switchable, CD123-directed UniCAR T-cell product treating patients with acute myeloid leukaemia (AML) was reported. Relapsed and refractory AML is prone to high plasticity under therapy pressure targeting one single tumour antigen. Thus, targeting of multiple tumour antigens seems to be required to achieve durable anti-tumour responses, underlining the need to further design alternative AML-specific target modules (TM) for the UniCAR platform. We here present the preclinical development of a novel FMS-like tyrosine kinase 3 (FLT3)-directed UniCAR T-cell therapy, which is highly effective for in vitro killing of both AML cell lines and primary AML samples. Furthermore, we show in vivo functionality in a murine xenograft model. PET analyses further demonstrate a short serum half-life of FLT3 TMs, which will enable a rapid on/off switch of UniCAR T cells. Overall, the presented preclinical data encourage the further development and clinical translation of FLT3-specific UniCAR T cells for the therapy of AML.

Details

Original languageEnglish
Pages (from-to)1137-1150
Number of pages14
JournalBritish journal of haematology
Volume202
Issue number6
Publication statusPublished - Sept 2023
Peer-reviewedYes

External IDs

PubMed 37460273

Keywords

ASJC Scopus subject areas

Keywords

  • CAR T cells, CD135, FLT3, UniCAR, acute myeloid leukaemia, Antigens, Neoplasm, Immunotherapy, Adoptive, T-Lymphocytes, Humans, Leukemia, Myeloid, Acute/drug therapy, fms-Like Tyrosine Kinase 3/genetics, Animals, Mice