ArticleHaematologica2013
Complement factor H-derived short consensus repeat 18-20 enhanced complement-dependent cytotoxicity of ofatumumab on chronic lymphocytic leukemia cells.
Article in Haematologica, 2013. 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, 30 citations in OpenAlex.
- Directed-Complement Activation as a Novel Immunotherapeutic Approach for HER2-Breast Cancer.ImmunoTargets and therapy · 2025Article
- Enhancement of complement-dependent cytotoxicity by linking factor-H derived short consensus repeats 19-20 to CD20 antibodies.Frontiers in immunology · 2024Article
- The human factor H protein family - an update.Frontiers in immunology · 2024Review
- 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
- How Does Complement Affect Hematological Malignancies: From Basic Mechanisms to Clinical Application.Frontiers in immunology · 2020Review
- Article
- Complement Activation as a Helping Hand for Inflammophilic Pathogens and Cancer.Frontiers in immunology · 2018Review
- Article
- Targeted delivery of siRNA using transferrin-coupled lipoplexes specifically sensitizes CD71 high expressing malignant cells to antibody-mediated complement attack.Targeted oncology · 2015Article
- Neutralization of membrane complement regulators improves complement-dependent effector functions of therapeutic anticancer antibodies targeting leukemic cells.Oncoimmunology · 2015Article
- Monoclonal Antibodies in Cancer Therapy: Mechanisms, Successes and Limitations.The West Indian medical journal · 2014Article
- Novel bifunctional single-chain variable antibody fragments to enhance virolysis by complement: generation and proof-of-concept.BioMed research international · 2014Article
- Regulation of complement and modulation of its activity in monoclonal antibody therapy of cancer.mAbs · 2014Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The antitumor activity of monoclonal antibodies in the treatment of chronic lymphocytic leukemia is mediated mainly by antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Unfortunately, the efficacy of complement-dependent cytotoxicity is strongly restricted due to the expression and acquisition of regulators of complement activation by lymphocytic leukemia cells. Whereas the role of membrane regulators of complement activation, such as CD55 and CD59, has been investigated in detail in chronic lymphocytic leukemia, the involvement of soluble regulators of complement activation, such as complement factor H, has not yet been reported. Propidium iodide staining was performed to investigate the efficacy of ofatumumab and factor H-derived short-consensus-repeat 18-20 in the induction of complement-dependent cytotoxicity on primary chronic lymphocytic leukemia cells from 20 patients. Deposition of complement C3 fragments was monitored by western blot analysis. Expression of CD20, CD55 or CD59 was determined by FACS analysis. Replacement of factor H with short consensus repeat 18-20 significantly increased the susceptibility of primary chronic lymphocytic leukemia cells to ofatumumab-induced complement-dependent cytotoxicity. More importantly, addition of short-consensus-repeat 18-20 was able to overcome complement- resistance occurring during treatment with ofatumumab alone. Use of short consensus repeat 18-20 is likely to prolong the turnover time of active C3b fragments generated on the target cells following ofatumumab-induced complement activation, thereby improving specific killing of chronic lymphocytic leukemia cells by complement-dependent cytotoxicity. The relative contribution of factor H to the protection of chronic lymphocytic leukemia cells against complement-dependent cytotoxicity was comparable to that of CD55. Our data suggest that, by abrogating factor H function, short consensus repeat 18-20 may provide a novel approach that improves the complement-dependent efficacy of therapeutic monoclonal antibodies.
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