ArticleTargeted oncology2016
Novel TNF-related Apoptotic-inducing Ligand-based Immunotoxin for Therapeutic Targeting of CD25 Positive Leukemia.
Article in Targeted oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 17 citations in OpenAlex.
- Curcumin and Acute Myeloid Leukemia: Synergistic Effects with Targeted Therapy.International journal of molecular sciences · 2025Review
- Turn TRAIL Into Better Anticancer Therapeutic Through TRAIL Fusion Proteins.Cancer medicine · 2025Review
- Application of an Autoinduction Strategy to Optimize the Heterologous Production of an Antitumor Bispecific Fusion Protein Based on the TRAIL Receptor-Selective Mutant Variant in Escherichia coli.Molecular biotechnology · 2023Article
- Review
- Structure-Activity Relationship of the Dimeric and Oligomeric Forms of a Cytotoxic Biotherapeutic Based on Diphtheria Toxin.Biomolecules · 2022Article
- Optimized Heterologous Expression and Efficient Purification of a New TRAIL-Based Antitumor Fusion Protein SRH-DR5-B with Dual VEGFR2 and DR5 Receptor Specificity.International journal of molecular sciences · 2022Article
- Molecular Mode of Action of TRAIL Receptor Agonists-Common Principles and Their Translational Exploitation.Cancers · 2019Review
- Antibodies and Derivatives Targeting DR4 and DR5 for Cancer Therapy.Antibodies (Basel, Switzerland) · 2017Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHuman TNF-related apoptotic-inducing ligand (TRAIL) has been used successfully for targeted therapy of almost all cancers. Leukemia is the most common type of cancer in children, and despite the advances in therapeutic strategies, the survival rate in leukemia cases is very low. Overexpression of interleukin 2 receptor (IL2R) in hematological malignancies has been utilized to target leukemia. Here, we report an immunotoxin fusion construct of human IL2α and TRAIL for targeting leukemia.
aimOur aim was to develop an immunotoxin to target CD25+ leukemic cells.
methodsRecombinant fusion construct comprising human IL2α and TRAIL114-281 was cloned, expressed and purified. Surface expression levels of IL2α and TRAIL receptors (CD25 and DR5 respectively) were compared in four leukemic cell lines and patient-derived peripheral blood mononuclear cells (PBMCs). Efficacy of immunotoxins was tested in cell lines and PBMCs by cell viability assay and compared with receptor expression.
resultsThe efficacy of IL2-TRAIL was higher than TRAIL alone and showed an IC50 ranging from 0.2-0.8 μM in cell lines. IL2-TRAIL induced cell death in PBMCs from leukemic patients in vitro, which was proportional to CD25 expression. Out of 34 leukemic samples, 24 samples were susceptible to immunotoxin-mediated cytotoxicity. The efficacy of IL2-TRAIL (87.5 %) was significantly high compared to TRAIL protein (29 %) in both myeloid and lymphoid leukemic patient samples. IL2-TRAIL fusion protein was highly specific for CD25+ leukemia and showed 100 % efficacy in lymphocytic leukemia [acute lymphoblastic leukemia and chronic lymphocytic leukemia] that overexpressed CD25.
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