ArticleOncoimmunology2021
Cyclophosphamide alters the tumor cell secretome to potentiate the anti-myeloma activity of daratumumab through augmentation of macrophage-mediated antibody dependent cellular phagocytosis.
Article in Oncoimmunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Optimal daratumumab-based regimen for patients with newly diagnosed and previously untreated multiple myeloma: systematic review and component network meta-analysis.Systematic reviews · 2025Pooled it
- Superior 12-month progression-free survival with frontline DVd versus VRd in patients with newly diagnosed multiple myeloma: a multicenter propensity score-matched analysis.Journal of translational medicine · 2026Observational
- Daratumumab-based quadruplet for patients with extramedullary multiple myeloma: Results from the Phase II prospective EMN19 study.HemaSphere · 2026Article
- Patient-derived ovarian cancer models demonstrate the influence of tumor-associated macrophages on therapeutic response.Oncoimmunology · 2025Article
- Chemotherapy drugs do not affect the production of hepatitis B surface antibodies: A case report.Oncology letters · 2025Article
- Essential thrombocythemia as an initial presentation of polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome with complete response to the bortezomib, cyclophosphamide, dexamethasone regimen: a case report.Journal of medical case reports · 2025Article
- Targeting prostate cancer by new bispecific monocyte engager directed to prostate-specific membrane antigen.PloS one · 2025Article
- Article
- Review
- Bispecific Antibodies in Multiple Myeloma: Opportunities to Enhance Efficacy and Improve Safety.Cancers · 2023Review
- The protective effects of rutin on the liver, kidneys, and heart by counteracting organ toxicity caused by synthetic and natural compounds.Food science & nutrition · 2023Review
- Tumor-Associated Macrophages and Related Myelomonocytic Cells in the Tumor Microenvironment of Multiple Myeloma.Cancers · 2022Review
- Low anti-CFL1 antibody with high anti-ACTB antibody is a poor prognostic factor in esophageal squamous cell carcinoma.Esophagus : official journal of the Japan Esophageal Society · 2022Article
- Vascular normalization and immunotherapy: Spawning a virtuous cycle.Frontiers in oncology · 2022Review
- Mechanisms of Immune Evasion in Multiple Myeloma: Open Questions and Therapeutic Opportunities.Cancers · 2021Review
- Induction Treatment in Transplant-eligible Multiple Myeloma.HemaSphere · 2021Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple Myeloma (MM) is a malignant disorder of plasma cells which, despite significant advances in treatment, remains incurable. Daratumumab, the first CD38 directed monoclonal antibody, has shown promising activity alone and in combination with other agents for MM treatment. Daratumumab is thought to have pleiotropic mechanisms of activity including natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC). With the knowledge that CD38-expressing NK cells are depleted by daratumumab, we sought to investigate a potential mechanism of enhancing macrophage-mediated antibody-dependent cellular phagocytosis (ADCP) by combining daratumumab with cyclophosphamide (CTX). Cyclophosphamide's immunomodulatory function was investigated by conditioning macrophages with tumor cell secretome collected from cyclophosphamide treated MM cell lines (CTX-TCS). Flow cytometry analysis revealed that CTX-TCS conditioning augmented the migratory capacity of macrophages and increased CD32 and CD64 Fcγ receptor expression on their cell surface. Daratumumab-specific tumor clearance was increased by conditioning macrophages with CTX-TCS in a dose-dependent manner. This effect was impeded by pre-incubating macrophages with Cytochalasin D (CytoD), an inhibitor of actin polymerization, indicating macrophage-mediated ADCP as the mechanism of clearance. CD64 expression on macrophages directly correlated with MM cell clearance and was essential to the observed synergy between cyclophosphamide and daratumumab, as tumor clearance was attenuated in the presence of a FcγRI/CD64 blocking agent. Cyclophosphamide independently enhances daratumumab-mediated killing of MM cells by altering the tumor microenvironment to promote macrophage recruitment, polarization to a pro-inflammatory phenotype, and directing ADCP. These findings support the addition of cyclophosphamide to existing or novel monoclonal antibody-containing MM regimens.
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Registered trials
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