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A Humanized Anti-CD22-Onconase Antibody-Drug Conjugate Mediates Highly Potent Destruction of Targeted Tumor Cells
المؤلفون المشاركون
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
المصدر
Journal of Immunology Research
العدد
المجلد 2015، العدد 2015 (31 ديسمبر/كانون الأول 2015)، ص ص. 1-14، 14ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2015-10-28
دولة النشر
مصر
عدد الصفحات
14
التخصصات الرئيسية
الملخص 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.
نمط استشهاد جمعية علماء النفس الأمريكية (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
نمط استشهاد الجمعية الأمريكية للغات الحديثة (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
نمط استشهاد الجمعية الطبية الأمريكية (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
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-1068520
قاعدة معامل التأثير والاستشهادات المرجعية العربي "ارسيف Arcif"
أضخم قاعدة بيانات عربية للاستشهادات المرجعية للمجلات العلمية المحكمة الصادرة في العالم العربي
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