CLEVER-1 targeting antibody, bexmarilimab, supports HLA-DR expression and alters ex vivo responsiveness to azacitidine and venetoclax in myeloid malignancies - UTU Research Portal

A1 Refereed original research article in a scientific journal

CLEVER-1 targeting antibody, bexmarilimab, supports HLA-DR expression and alters ex vivo responsiveness to azacitidine and venetoclax in myeloid malignancies

Authors: Aakko, Sofia; Ylitalo, Arno; Kuusanmäki, Heikki; Rannikko, Jenna H.; Björkman, Mari; Mandelin, Jami; Heckman, Caroline A.; Kontro, Mika; Hollmén, Maija

Publisher: Springer Science and Business Media LLC

Publishing place: BERLIN

Publication year: 2025

Journal: Scientific Reports

Journal name in source: Scientific Reports

Journal acronym: SCI REP-UK

Article number: 16775

Volume: 15

Issue: 1

Number of pages: 13

ISSN: 2045-2322

eISSN: 2045-2322

DOI: https://doi.org/10.1038/s41598-025-01675-y

Web address : https://doi.org/10.1038/s41598-025-01675-y

Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/498613459

Abstract

Treatment of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) requires new therapy options, especially for patients uneligible for intense chemotherapy or with relapsed or refractory disease. CLEVER-1 is a myeloid checkpoint protein, which can be targeted with a therapeutic function blocking antibody, bexmarilimab. Bexmarilimab has shown clinical efficacy in different solid tumors. Here, we show preclinical data demonstrating expression of CLEVER-1 on immature malignant myeloid cells and their derivates in MDS and AML bone marrow samples and AML cell lines. Highest CLEVER-1 levels were observed in AML with monocytic differentiation. Ex vivo treatment of AML/MDS bone marrow samples with bexmarilimab led to an increase in antigen-presenting human leukocyte antigen DR isotype (HLA-DR) molecule expression. Combination of bexmarilimab with current standard-of-care (SoC) drugs, azacitidine and venetoclax, showed potential for HLA-DR induction and enhanced killing of leukemic cells, respectively. Our non-clinical findings support the feasibility of CLEVER-1 inhibition in AML/MDS to induce antigen presentating molecule expression and potentially, an anti-leukemic effect together with SoC. Therapeutic targeting of CLEVER-1 with bexmarilimab is currently undergoing clinical investigation in the BEXMAB trial (NCT05428969).

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Funding information in the publication:
This study was supported by Post Docs in Companies grant from the Finnish Cultural Foundation to SA, Business Finland funding 8040/31/2019 (Cancer IO) to Faron Pharmaceuticals, Finnish Medical Foundation and Cancer Foundation Finland to MK, and Academy of Finland fellowship funding and Sigrid Jusélius grant to MH. The FIMM High Throughput Biomedicine Unit is financially supported by the University of Helsinki (HiLIFE) and Biocenter Finland.