ArticleFrontiers in immunology2020
Isatuximab Acts Through Fc-Dependent, Independent, and Direct Pathways to Kill Multiple Myeloma Cells.
Article in Frontiers in immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 111 citations in OpenAlex.
- Biological research on the occurrence and development of multiple myeloma and its treatment.Immunity, inflammation and disease · 2023Pooled it
- Clinical Validation of a QSP Model for ISB 2001, a Trispecific T Cell Engager to Support Optimal FIH Study Design in RRMM Patients.Clinical pharmacology and therapeutics · 2026Trial
- Efficacy and safety of isatuximab subcutaneous plus carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma: results of the Phase 2 study IZALCO.Blood cancer journal · 2025Trial
- Isatuximab plus bortezomib, lenalidomide, and dexamethasone for transplant-ineligible newly diagnosed multiple myeloma patients: a frailty subgroup analysis of the IMROZ trial.Haematologica · 2025Trial
- Allocation and validation of the second revision of the International Staging System in the ICARIA-MM and IKEMA studies.Blood cancer journal · 2024Trial
- Trial
- Isatuximab, carfilzomib, and dexamethasone in patients with relapsed multiple myeloma: updated results from IKEMA, a randomized Phase 3 study.Blood cancer journal · 2023Trial
- Isatuximab in combination with cemiplimab in patients with relapsed/refractory multiple myeloma: A phase 1/2 study.Cancer medicine · 2023Trial
- A phase 1/2, open-label, multicenter study of isatuximab in combination with cemiplimab in patients with lymphoma.Hematological oncology · 2023Trial
- Isatuximab monotherapy in patients with refractory T-acute lymphoblastic leukemia or T-lymphoblastic lymphoma: Phase 2 study.Cancer medicine · 2022Trial
- Targeting CD38 and PD-1 with isatuximab plus cemiplimab in patients with advanced solid malignancies: results from a phase I/II open-label, multicenter study.Journal for immunotherapy of cancer · 2022Trial
- Emerging organoids and organoids-on-chip platforms for translational development of antibody‒drug conjugates and next-generation bioconjugates.Acta pharmaceutica Sinica. B · 2026Review
- Review
- Isatuximab: A Review in Transplant-Ineligible Newly Diagnosed Multiple Myeloma.Targeted oncology · 2026Review
- Multifunctional CD38 in the pathogenesis and treatment of B-cell lymphomas.American journal of blood research · 2026Review
- FOXM1 down-regulation is a trigger of isatuximab-induced direct cell death in multiple myeloma cells with 1q.Haematologica · 2026Article
- The real-world safety profile and potential mechanism of isatuximab: Integration of pharmacovigilance and transcriptomic analysis.Medicine · 2025Article
- Immunotherapy in multiple myeloma: advances from immune microenvironment insights to clinical application.Molecular biology reports · 2025Review
- Article
- Non-Competitive Binding of Isatuximab and Daratumumab to CD38: Implications for Targeted Therapy in Multiple Myeloma.Pharmaceutics · 2025Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Isatuximab is a monoclonal antibody targeting the transmembrane receptor and ectoenzyme CD38, a protein highly expressed on hematological malignant cells, including those in multiple myeloma (MM). Upon binding to CD38-expressing MM cells, isatuximab is thought to induce tumor cell killing via fragment crystallizable (Fc)-dependent mechanisms, including antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC), as well as via direct Fc-independent mechanisms. Here, these mechanisms of action were investigated in MM and diffuse large B-cell lymphoma (DLBCL) cell lines, as well as in peripheral blood mononuclear cells derived from healthy donors, and in MM patient-derived samples. Our findings show that isatuximab-mediated cytotoxicity occurred primarily via ADCC and ADCP in MM cell lines and via ADCC and apoptosis in DLBCL cell lines expressing high levels of CD38. We identified the programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) pathway and MM cell-secreted transforming growth factor-beta (TGF-β) as tumor cell-related features that could suppress CD38-mediated ADCC. Furthermore, we established that isatuximab can directly activate natural killer (NK) cells and promote NK cell-mediated cytotoxicity via crosslinking of CD38 and CD16. Finally, isatuximab-induced CDC was observed in cell lines with high CD38 receptor density (>250,000 molecules/cell) and limited expression of inhibitory complement regulatory proteins (CD46, CD55, and CD59; <50,000 molecules/cell). Taken together, our findings highlight mechanistic insights for isatuximab and provide support for a range of combination therapy approaches that could be tested for isatuximab in the future.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.