ArticleJournal of immunology research2015
A Humanized Anti-CD22-Onconase Antibody-Drug Conjugate Mediates Highly Potent Destruction of Targeted Tumor Cells.
Article in Journal of immunology research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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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
12 citing papers in PubMed, 26 citations in OpenAlex.
- Preparation, expression, and anti-cancer effects of the novel fusion protein rONC-T7-pHLIP.Applied microbiology and biotechnology · 2025Article
- EGFR-targeting RNase A-cetuximab antibody-drug conjugate induces ROS-mediated apoptosis to overcome drug resistance in KRAS mutant cancer cells.Scientific reports · 2025Article
- Potent anti-tumor activity of CD45RA-targeting Hm3A4-Ranpirnase against myeloid lineage leukemias.Bioengineered · 2022Article
- Dimerization of Human Angiogenin and of Variants Involved in Neurodegenerative Diseases.International journal of molecular sciences · 2021Article
- Engineered scPDL1-DM1 drug conjugate with improved in vitro analysis to target PD-L1 positive cancer cells and intracellular trafficking studies in cancer therapy.Genetics and molecular biology · 2020Article
- Antibody-Mediated Enzyme Therapeutics and Applications in Glycogen Storage Diseases.Trends in molecular medicine · 2019Review
- Acquired Resistance to Antibody-Drug Conjugates.Cancers · 2019Review
- Updates in the Development of ImmunoRNases for the Selective Killing of Tumor Cells.Biomedicines · 2018Review
- Immune Modulation by Human Secreted RNases at the Extracellular Space.Frontiers in immunology · 2018Review
- A novel anti-CD22 scFv-apoptin fusion protein induces apoptosis in malignant B-cells.AMB Express · 2017Article
- Addressing the Immunogenicity of the Cargo and of the Targeting Antibodies with a Focus on Demmunized Bacterial Toxins and on Antibody-Targeted Human Effector Proteins.Biomedicines · 2017Review
- Two Saporin-Containing Immunotoxins Specific for CD20 and CD22 Show Different Behavior in Killing Lymphoma Cells.Toxins · 2017Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
Antibody-drug conjugates (ADCs) have evolved as a new class of potent cancer therapeutics. We here report on the development of ADCs with specificity for the B-cell lineage specific (surface) antigen CD22 being expressed in the majority of hematological malignancies. As targeting moiety a previously generated humanized anti-CD22 single-chain variable fragment (scFv) derivative from the monoclonal antibody RFB4 was reengineered into a humanized IgG1 antibody format (huRFB4). Onconase (ranpirnase), a clinically active pancreatic-type ribonuclease, was employed as cytotoxic payload moiety. Chemical conjugation via thiol-cleavable disulfide linkage retained full enzymatic activity and full binding affinity of the ADC. Development of sophisticated purification procedures using size exclusion and ion exchange chromatography allowed the separation of immunoconjugate species with stoichiometrically defined number of Onconase cargos. A minimum of two Onconase molecules per IgG was required for achieving significant in vitro cytotoxicity towards lymphoma and leukemia cell lines. Antibody-drug conjugates with an Onconase to antibody ratio of 3 : 1 exhibited an IC50 of 0.08 nM, corresponding to more than 18,400-fold increased cytotoxicity of the ADC when compared with unconjugated Onconase. These results justify further development of this ADC as a promising first-in-class compound for the treatment of CD22-positive malignancies.
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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.