ArticlePloS one2015
Reformatting Rituximab into Human IgG2 and IgG4 Isotypes Dramatically Improves Apoptosis Induction In Vitro.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 28 citations in OpenAlex.
- Targeting CD20 for B-cell Depletion in Autoimmune Kidney Disease: Next Generation.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Review
- Rituximab-IgG2 is a phagocytic enhancer in antibody-based immunotherapy of B-cell lymphoma by altering CD47 expression.Frontiers in immunology · 2024Article
- Using adjusted local assortativity with Molecular Pixelation unveils colocalization of membrane proteins with immunological significance.Frontiers in immunology · 2024Article
- The selection of variable regions affects effector mechanisms of IgA antibodies against CD20.Blood advances · 2021Article
- Engineering a human IgG2 antibody stable at low pH.Protein science : a publication of the Protein Society · 2020Article
- Harnessing the immune system via FcγR function in immune therapy: a pathway to next-gen mAbs.Immunology and cell biology · 2020Review
- Article
- Antibody Structure and Function: The Basis for Engineering Therapeutics.Antibodies (Basel, Switzerland) · 2019Review
- Anti-CD20 Directed Therapy of B Cell Lymphomas: Are New Agents Really Better?Current oncology reports · 2018Review
- Antibody-dependent cell-mediated cytotoxicity induced by active immunotherapy based on racotumomab in non-small cell lung cancer patients.Cancer immunology, immunotherapy : CII · 2018Article
- Antibody Isotypes for Tumor Immunotherapy.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2017Review
- Article
- Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The direct induction of cell death, or apoptosis, in target cells is one of the effector mechanisms for the anti CD20 antibody Rituximab. Here we provide evidence that Rituximab's apoptotic ability is linked to the antibody IgG isotype. Reformatting Rituximab from the standard human IgG1 heavy chain into IgG2 or IgG4 boosted in vitro apoptosis induction in the Burkitt's lymphoma B cell line Ramos five and four-fold respectively. The determinants for this behavior are located in the hinge region and CH1 domain of the heavy chain. By transplanting individual IgG2 or IgG4 specific amino acid residues onto otherwise IgG1 like backbones, thereby creating hybrid antibodies, the same enhancement of apoptosis induction could be achieved. The cysteines at position 131 of the CH1 domain and 219 in the hinge region, involved in IgG2 and IgG4 disulfide formation, were found to be of particular structural importance. Our data indicates that the hybrid antibodies possess a different CD20 binding mode than standard Rituximab, which appears to be key in enhancing apoptotic ability. The presented work opens up an interesting engineering route for enhancing the direct cytotoxic ability of therapeutic antibodies.
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