ArticleClinical and experimental immunology2007
Down-regulation of CD55 and CD46 expression by anti-sense phosphorothioate oligonucleotides (S-ODNs) sensitizes tumour cells to complement attack.
Article in Clinical and experimental immunology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 60 citations in OpenAlex.
- CD55 may be a new target for colorectal cancer treatment.Scientific reports · 2025Article
- Chemotherapy of breast cancer cells alters susceptibility to complement-mediated opsonization and killing.Medical oncology (Northwood, London, England) · 2025Article
- CD55 in cancer: Complementing functions in a non-canonical manner.Cancer letters · 2022Review
- Therapeutic Lessons to be Learned From the Role of Complement Regulators as Double-Edged Sword in Health and Disease.Frontiers in immunology · 2020Review
- Flow cytometry-based assessment of direct-targeting anti-cancer antibody immune effector functions.Methods in enzymology · 2020Article
- Complement C5b-9 and Cancer: Mechanisms of Cell Damage, Cancer Counteractions, and Approaches for Intervention.Frontiers in immunology · 2019Review
- The Role of Membrane Bound Complement Regulatory Proteins in Tumor Development and Cancer Immunotherapy.Frontiers in immunology · 2019Review
- The complement system in the airway epithelium: An overlooked host defense mechanism and therapeutic target?The Journal of allergy and clinical immunology · 2018Review
- Cooperation between Hsp90 and mortalin/GRP75 in resistance to cell death induced by complement C5b-9.Cell death & disease · 2018Article
- Beyond the Role of CD55 as a Complement Component.Immune network · 2018Review
- Complement in cancer: untangling an intricate relationship.Nature reviews. Immunology · 2018Review
- Oligonucleotide modifications enhance probe stability for single cell transcriptome in vivo analysis (TIVA).Organic & biomolecular chemistry · 2017Article
- CD55 and CD59 expression protects HER2-overexpressing breast cancer cells from trastuzumab-induced complement-dependent cytotoxicity.Oncology letters · 2017Article
- The dual role of complement in cancer and its implication in anti-tumor therapy.Annals of translational medicine · 2016Review
- Article
- Chronic Activation of Innate Immunity Correlates With Poor Prognosis in Cancer Patients Treated With Oncolytic Adenovirus.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Preclinical safety, pharmacokinetics, pharmacodynamics, and biodistribution studies with Ad35K++ protein: a novel rituximab cotherapeutic.Molecular therapy. Methods & clinical development · 2016Article
- 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
- Complement factor H polymorphism rs1061170 and the effect of cigarette smoking on the risk of lung cancer.Contemporary oncology (Poznan, Poland) · 2015Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Overexpression of one or more membrane-bound complement regulatory proteins (mCRPs) protects tumour cells against complement-mediated clearance by the autologous humoral immune response and is also considered as a barrier for successful immunotherapy with monoclonal anti-tumour antibodies. Neutralization of mCRPs by blocking antibodies, enzymatic removal or cytokine-mediated down-regulation has been shown to sensitize tumour cells to complement attack. In our study we applied, for the first time, anti-sense phosphorothioate oligonucleotides (S-ODNs) to knock down the expression of the mCRPs CD55 and CD46 with the aim of exploiting complement more effectively for tumour cell damage. Potent anti-sense oligonucleotides against CD55 and CD46 were identified by screening various target sequences (n = 10) for each regulator. S-ODN anti-CD55(687) reduced CD55 protein expression up to 84% and CD46 protein expression was inhibited up to 76% by S-ODN anti-CD46(85). Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed a similar reduction of the CD55 and CD46 mRNA levels, which argues for an RNAse H-dependent anti-sense mechanism. T47D, A549 and PC3 cells, representing breast, lung and prostate carcinoma, were used for functional studies. Dependent on the particular cell line, anti-sense-based inhibition of mCRP expression enhanced complement-dependent cytolysis (CDC) up to 42% for CD55 and up to 40% for CD46, and the combined inhibition of both regulators yielded further additive effects in T47D cells. C3 opsonization of CD55/CD46-deficient tumour cells was also clearly enhanced upon mCRP suppression. Due to the clinical applicability of S-ODNs, the anti-sense approach described in this study may offer an additional alternative to improve the efficacy of antibody- and complement-based cancer immunotherapy.
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