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A Humanized Anti-CD22-Onconase Antibody-Drug Conjugate Mediates Highly Potent Destruction of Targeted Tumor Cells
Joint Authors
Jaeger, Dirk
Weber, Tobias
Mavratzas, Athanasios
Kiesgen, Stefan
Haase, Stephanie
Bötticher, Benedikt
Exner, Evelyn
Mier, Walter
Grosse-Hovest, Ludger
Arndt, Michaela A. E.
Krauss, Jürgen
Source
Journal of Immunology Research
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-10-28
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Weber, Tobias& Mavratzas, Athanasios& Kiesgen, Stefan& Haase, Stephanie& Bötticher, Benedikt& Exner, Evelyn…[et al.]. 2015. A Humanized Anti-CD22-Onconase Antibody-Drug Conjugate Mediates Highly Potent Destruction of Targeted Tumor Cells. Journal of Immunology Research،Vol. 2015, no. 2015, pp.1-14.
https://search.emarefa.net/detail/BIM-1068520
Modern Language Association (MLA)
Weber, Tobias…[et al.]. A Humanized Anti-CD22-Onconase Antibody-Drug Conjugate Mediates Highly Potent Destruction of Targeted Tumor Cells. Journal of Immunology Research No. 2015 (2015), pp.1-14.
https://search.emarefa.net/detail/BIM-1068520
American Medical Association (AMA)
Weber, Tobias& Mavratzas, Athanasios& Kiesgen, Stefan& Haase, Stephanie& Bötticher, Benedikt& Exner, Evelyn…[et al.]. A Humanized Anti-CD22-Onconase Antibody-Drug Conjugate Mediates Highly Potent Destruction of Targeted Tumor Cells. Journal of Immunology Research. 2015. Vol. 2015, no. 2015, pp.1-14.
https://search.emarefa.net/detail/BIM-1068520
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1068520