ArticleFrontiers in immunology2022
Myeloid checkpoint blockade improves killing of T-acute lymphoblastic leukemia cells by an IgA2 variant of daratumumab.
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 15 citations in OpenAlex.
- Myeloid cell-mediated killing of B-ALL by CD38 and CD20 IgA antibody variants is enhanced by CD47/SIRPα interference.Blood neoplasia · 2026Article
- Retargeted adenoviruses for local IgA and CD47 blocker production as a novel cancer therapy.EMBO molecular medicine · 2026Article
- Engineering of anticancer human immunoglobulin A equipped with albumin for enhanced plasma half-life.PNAS nexus · 2025Article
- The relevance of tumor target expression levels on IgA-mediated cytotoxicity in cancer immunotherapy.Cancer immunology, immunotherapy : CII · 2024Article
- Enhancing IgA-mediated neutrophil cytotoxicity against neuroblastoma by CD47 blockade.Journal for immunotherapy of cancer · 2024Article
- Frequent, high density expression of surface CD38 as a potential therapeutic target in adult T-lineage acute lymphoblastic leukemia.Haematologica · 2024Article
- Sialylation inhibition improves macrophage mediated tumor cell phagocytosis of breast cancer cells triggered by therapeutic antibodies of different isotypes.Frontiers in oncology · 2024Article
- All-trans retinoic acid in hematologic disorders: not just acute promyelocytic leukemia.Frontiers in pharmacology · 2024Review
- Review
- Mitogen-Activated Protein Kinase and Nuclear Hormone Receptor Crosstalk in Cancer Immunotherapy.International journal of molecular sciences · 2023Review
- Characterization of human Fc alpha receptor transgenic mice: comparison of CD89 expression and antibody-dependent tumor killing between mouse strains.Cancer immunology, immunotherapy : CII · 2023Article
- Deciphering the role of QPCTL in glioma progression and cancer immunotherapy.Frontiers in immunology · 2023Article
- Dual checkpoint blockade of CD47 and LILRB1 enhances CD20 antibody-dependent phagocytosis of lymphoma cells by macrophages.Frontiers in immunology · 2022Article
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antibody-based immunotherapy is increasingly employed to treat acute lymphoblastic leukemia (ALL) patients. Many T-ALL cells express CD38 on their surface, which can be targeted by the CD38 antibody daratumumab (DARA), approved for the treatment of multiple myeloma. Tumor cell killing by myeloid cells is relevant for the efficacy of many therapeutic antibodies and can be more efficacious with human IgA than with IgG antibodies. This is demonstrated here by investigating antibody-dependent cellular phagocytosis (ADCP) by macrophages and antibody-dependent cell-mediated cytotoxicity (ADCC) by polymorphonuclear (PMN) cells using DARA (human IgG1) and an IgA2 isotype switch variant (DARA-IgA2) against T-ALL cell lines and primary patient-derived tumor cells. ADCP and ADCC are negatively regulated by interactions between CD47 on tumor cells and signal regulatory protein alpha (SIRPα) on effector cells. In order to investigate the impact of this myeloid checkpoint on T-ALL cell killing, CD47 and glutaminyl-peptide cyclotransferase like (QPCTL) knock-out T-ALL cells were employed. QPTCL is an enzymatic posttranslational modifier of CD47 activity, which can be targeted by small molecule inhibitors. Additionally, we used an IgG2σ variant of the CD47 blocking antibody magrolimab, which is in advanced clinical development. Moreover, treatment of T-ALL cells with all-
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