ArticleLeukemia2012
The novel calicheamicin-conjugated CD22 antibody inotuzumab ozogamicin (CMC-544) effectively kills primary pediatric acute lymphoblastic leukemia cells.
Article in Leukemia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 114 citations in OpenAlex.
- Efficacy of Targeted Immunotherapy as Induction or Salvage Therapy in Acute Lymphoblastic Leukemia: A Systematic Review and Meta-Analysis.Technology in cancer research & treatmentPooled it
- Effect of inotuzumab ozogamicin on the QT interval in patients with haematologic malignancies using QTc-concentration modelling.British journal of clinical pharmacology · 2019Trial
- Targeting drug efflux and DNA repair enhances inotuzumab ozogamicin activity in IO-resistant B-ALL cell lines.International journal of hematology · 2026Article
- Therapeutic Advances in Adult B-cell Acute Lymphoblastic Leukemia with KMT2A Rearrangements.Annals of hematology · 2026Review
- A review of treatment strategies for elderly patients with Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia.Translational oncology · 2026Review
- Inotuzumab ozogamicin combined with chemotherapy in pediatric B-cell precursor CD22Haematologica · 2024Article
- Treatment of Relapsed Acute Lymphocytic Leukemia in Adult Patients.Current treatment options in oncology · 2024Review
- Population Pharmacokinetics of Inotuzumab Ozogamicin in Pediatric Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia: Results of Study ITCC-059.Clinical pharmacokinetics · 2024Article
- Inotuzumab Ozogamicin: First Pediatric Approval.Paediatric drugs · 2024Review
- Naked antibodies and antibody-drug conjugates: targeted therapy for childhood acute lymphoblastic leukemia.Haematologica · 2024Review
- Inotuzumab ozogamicin for the treatment of adult acute lymphoblastic leukemia: past progress, current research and future directions.Journal of hematology & oncology · 2024Review
- Therapeutic antibodies for the prevention and treatment of cancer.Journal of biomedical science · 2024Review
- Aiming the magic bullet: targeted delivery of imaging and therapeutic agents to solid tumors by pHLIP peptides.Frontiers in pharmacology · 2024Review
- Dynemicin A Derivatives as Potential Cancer Chemotherapeutics by Mutasynthesis.Helvetica chimica acta · 2023Article
- Targeting CD22 for B-cell hematologic malignancies.Experimental hematology & oncology · 2023Review
- Antibody-Drug Conjugates in Solid Tumor Oncology: An Effectiveness Payday with a Targeted Payload.Pharmaceutics · 2023Review
- Binding domain on CD22 molecules contributing to the biological activity of T cell-engaging bispecific antibodies.Heliyon · 2023Article
- Pediatric Acute Lymphoblastic Leukemia Emerging Therapies-From Pathway to Target.International journal of molecular sciences · 2023Review
- Inotuzumab ozogamicin in B-cell precursor acute lymphoblastic leukemia: efficacy, toxicity, and practical considerations.Frontiers in immunology · 2023Review
- Indispensable role of microbes in anticancer drugs and discovery trends.Applied microbiology and biotechnology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We investigated whether the newly developed antibody (Ab) -targeted therapy inotuzumab ozogamicin (CMC-544), consisting of a humanized CD22 Ab linked to calicheamicin, is effective in pediatric primary B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells in vitro, and analyzed which parameters determine its efficacy. CMC-544 induced dose-dependent cell kill in the majority of BCP-ALL cells, although IC(50) values varied substantially (median 4.8 ng/ml, range 0.1-1000 ng/ml at 48 h). The efficacy of CMC-544 was highly dependent on calicheamicin sensitivity and CD22/CMC-544 internalization capacity of BCP-ALL cells, but hardly on basal and renewed CD22 expression. Although CD22 expression was essential for uptake of CMC-544, a repetitive loop of CD22 saturation, CD22/CMC-544 internalization and renewed CD22 expression was not required to achieve intracellular threshold levels of calicheamicin sufficient for efficient CMC-544-induced apoptosis in BCP-ALL cells. This is in contrast to studies with the comparable CD33 immunotoxin gemtuzumab ozogamicin (Mylotarg) in acute myeloid leukemia (AML) patients, in which complete and prolonged CD33 saturation was required for apoptosis induction. These data suggest that CMC-544 treatment may result in higher response rates in ALL compared with response rates obtained in AML with Mylotarg, and that therefore clinical studies in ALL, preferably with multiple low CMC-544 dosages, are warranted.
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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.