ArticleLeukemia2009
A novel AML-selective TRAIL fusion protein that is superior to Gemtuzumab Ozogamicin in terms of in vitro selectivity, activity and stability.
Article in Leukemia, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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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
31 citing papers in PubMed, 63 citations in OpenAlex.
- Turn TRAIL Into Better Anticancer Therapeutic Through TRAIL Fusion Proteins.Cancer medicine · 2025Review
- Recent advances in and applications of ex vivo drug sensitivity analysis for blood cancers.Blood research · 2024Review
- Beyond ADCs: harnessing bispecific antibodies to directly induce apoptosis for targeted tumor eradication.Antibody therapeutics · 2024Review
- Advances and Limitations of Antibody Drug Conjugates for Cancer.Biomedicines · 2021Review
- Article
- Molecular Mode of Action of TRAIL Receptor Agonists-Common Principles and Their Translational Exploitation.Cancers · 2019Review
- Antibody-drug conjugates: Promising and efficient tools for targeted cancer therapy.Journal of cellular physiology · 2018Review
- Factors Affecting the Pharmacology of Antibody-Drug Conjugates.Antibodies (Basel, Switzerland) · 2018Review
- Antibody-drug conjugates: recent advances in conjugation and linker chemistries.Protein & cell · 2018Review
- Anti-CD123 antibody-modified niosomes for targeted delivery of daunorubicin against acute myeloid leukemia.Drug delivery · 2017Article
- Antibodies and Derivatives Targeting DR4 and DR5 for Cancer Therapy.Antibodies (Basel, Switzerland) · 2017Review
- Advances in antibody-drug conjugates: A new era of targeted cancer therapy.Drug discovery today · 2017Review
- Complex effects of tumor microenvironment on the tumor disposition of carrier-mediated agents.Nanomedicine (London, England) · 2017Review
- Journey of TRAIL from Bench to Bedside and its Potential Role in Immuno-Oncology.Oncology reviews · 2017Review
- Novel TNF-related Apoptotic-inducing Ligand-based Immunotoxin for Therapeutic Targeting of CD25 Positive Leukemia.Targeted oncology · 2016Article
- Engineered adenovirus fiber shaft fusion homotrimer of soluble TRAIL with enhanced stability and antitumor activity.Cell death & disease · 2016Article
- Onto better TRAILs for cancer treatment.Cell death and differentiation · 2016Review
- Antibody-drug conjugates--an emerging class of cancer treatment.British journal of cancer · 2016Review
- Article
- Immunotoxins for leukemia.Blood · 2014Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gemtuzumab ozogamicin (GO, Mylotarg) is a targeted therapeutic agent in which an anti-CD33 antibody is chemically coupled to a highly cytotoxic calicheamicin derivative through a hydrolysable linker. GO has improved the treatment outcome for a subgroup of acute myeloid leukemia (AML) patients, but its use is associated with severe myelosuppression and hepatotoxicity. Here, we report on a novel anti-leukemia agent, designated scFvCD33:sTRAIL, in which an anti-CD33 single chain fragment of variable regions (scFv) antibody fragment is genetically linked to soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL). Normal CD33-positive monocytes were fully resistant to prolonged treatment with scFvCD33:sTRAIL, whereas treatment with GO resulted in substantial cytotoxicity. The activity of scFvCD33:sTRAIL towards AML cells was up to 30-fold higher than GO. The CD33-restricted anti-leukemia activity of scFvCD33:sTRAIL remained stable during prolonged storage at 37 degrees C, whereas GO showed a rapid increase in CD33-independent cytotoxicity. Moreover, scFvCD33:sTRAIL showed potent anti-leukemia activity towards CD33+ CML cells when treatment was combined with the Bcr-Abl tyrosine kinase inhibitor, Gleevec. Importantly, ex vivo treatment of patient-derived CD33+ AML tumor cells with scFvCD33:sTRAIL resulted in potent apoptosis induction that was enhanced by valproic acid, mitoxantrone and 17-(Allylamino)-17-demethoxygeldanamycin (17-AAG). Taken together, scFvCD33:sTRAIL is superior to GO in terms of tumor selectivity, activity and stability, warranting its further development for the treatment of CD33-positive leukemias.
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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.