ArticleHaematologica2010
HuMab-7D8, a monoclonal antibody directed against the membrane-proximal small loop epitope of CD20 can effectively eliminate CD20 low expressing tumor cells that resist rituximab-mediated lysis.
Article in Haematologica, 2010. 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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Who cites it
12 citing papers in PubMed, 32 citations in OpenAlex.
- Widespread Fab-arm exchange affects all endogenous serum IgG4.Nature communications · 2025Article
- Logic-gated antibody pairs that selectively act on cells co-expressing two antigens.Nature biotechnology · 2022Article
- The Role of Complement in the Mechanism of Action of Therapeutic Anti-Cancer mAbs.Antibodies (Basel, Switzerland) · 2020Review
- How Do mAbs Make Use of Complement to Kill Cancer Cells? The Role of CaAntibodies (Basel, Switzerland) · 2020Review
- Antibodies That Efficiently Form Hexamers upon Antigen Binding Can Induce Complement-Dependent Cytotoxicity under Complement-Limiting Conditions.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- De novo diffuse large B-cell lymphoma with a CD20 immunohistochemistry-positive and flow cytometry-negative phenotype: molecular mechanisms and correlation with rituximab sensitivity.Cancer science · 2014Article
- Complement factor H-derived short consensus repeat 18-20 enhanced complement-dependent cytotoxicity of ofatumumab on chronic lymphocytic leukemia cells.Haematologica · 2013Article
- Novel humanized anti-CD20 antibody BM-ca binds to a unique epitope and exerts stronger cellular activity than others.Cancer medicine · 2013Article
- Monoclonal antibodies and recombinant immunoglobulins for the treatment of multiple sclerosis.CNS drugs · 2012Review
- Epitope mapping of antibodies to VlsE protein of Borrelia burgdorferi in post-Lyme disease syndrome.Clinical immunology (Orlando, Fla.) · 2011Article
- Ongoing development of monoclonal antibodies and antibody drug-conjugates in lymphoma.Current oncology reports · 2011Article
- Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIncorporation of the chimeric CD20 monoclonal antibody rituximab in the treatment schedule of patients with non-Hodgkin's lymphoma has significantly improved outcome. Despite this success, about half of the patients do not respond to treatment or suffer from a relapse and additional therapy is required. A low CD20-expression level may in part be responsible for resistance against rituximab. We therefore investigated whether the CD20-expression level related resistance to rituximab could be overcome by a new group of CD20 mAbs (HuMab-7D8 and ofatumumab) targeting a unique membrane-proximal epitope on the CD20 molecule. DESIGN AND
methodsBy retroviral transduction of the CD20 gene into CD20-negative cells and clonal selection of transduced cells a system was developed in which the CD20-expression level is the only variable. These CD20 transduced cells were used to study the impact of rituximab and HuMab-7D8 mediated complement-dependent cytotoxicity. To study the in vivo efficacy of these mAbs an in vivo imaging system was generated by retroviral expression of the luciferase gene in the CD20-positive cells.
resultsWe show that HuMab-7D8 efficiently killed CD20(low) cells that are not susceptible to rituximab-induced killing in vitro. In a mouse xenograft model, we observed a comparable increase in survival time between HuMab-7D8 and rituximab-treated mice. Most significantly, however, HuMab-7D8 eradicated all CD20-expressing cells both in the periphery as well as in the bone marrow whereas after rituximab treatment CD20(low) cells survived.
conclusionsCells that are insensitive to in vitro and in vivo killing by rituximab as the result of their low CD20-expression profile may be efficiently killed by an antibody against the membrane-proximal epitope on CD20. Such antibodies should, therefore, be explored to overcome rituximab resistance in the clinic.
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