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Br J Haematol. 2019 May 23. doi: 10.1111/bjh.15975. [Epub ahead of print]

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

Author information

1
Medical Clinic and Polyclinic I, University Hospital 'Carl Gustav Carus', TU Dresden, Dresden, Germany.
2
Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Dresden, Germany.
3
German Cancer Consortium (DKTK), partner site Dresden, and German Cancer Centre (DKFZ), Heidelberg, Germany.
4
Institute of Immunology, Medical Faculty 'Carl Gustav Carus', TU Dresden, Dresden, Germany.
5
Centre for Regenerative Therapies Dresden, 'Carl Gustav Carus', TU Dresden, Dresden, Germany.
6
University Cancer Centre (UCC), 'Carl Gustav Carus', TU Dresden, Dresden, Germany.

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.

KEYWORDS:

T-cell based immunotherapy; acute myeloid leukaemia; combinatory therapy; midostaurin

PMID:
31119728
DOI:
10.1111/bjh.15975

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