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Midostaurin abrogates CD 33‐directed Uni CAR and CD 33‐ CD 3 bispecific antibody therapy in acute myeloid leukaemia
Author(s) -
Fasslrinner Frederick,
Arndt Claudia,
Koristka Stefanie,
Feldmann Anja,
Altmann Heidi,
von Bonin Malte,
Schmitz Marc,
Bornhäuser Martin,
Bachmann Michael
Publication year - 2019
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.15975
Subject(s) - midostaurin , immunotherapy , cd33 , cancer research , medicine , chimeric antigen receptor , antigen , tyrosine kinase , immunology , t cell , myeloid , antibody , myeloid leukemia , stem cell , immune system , biology , receptor , cd34 , genetics
Summary 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 CD 33. 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 FLT 3 TKI s for further clinical testing of combinatory approaches with T‐cell based immunotherapy.