ArticleMolecular therapy : the journal of the American Society of Gene Therapy2013
Transient removal of CD46 is safe and increases B-cell depletion by rituximab in CD46 transgenic mice and macaques.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 23 citations in OpenAlex.
- The multiverse of CD46 and oncologic interactions.The Journal of clinical investigation · 2025Review
- CD46 and CD59 inhibitors enhance complement-dependent cytotoxicity of anti-CD38 monoclonal antibodies daratumumab and isatuximab in multiple myeloma and other B-cell malignancy cells.Cancer biology & therapy · 2024Article
- Toward Overcoming Treatment Failure in Rheumatoid Arthritis.Frontiers in immunology · 2021Review
- CD46 and Oncologic Interactions: Friendly Fire against Cancer.Antibodies (Basel, Switzerland) · 2020Review
- The Role of Complement in the Mechanism of Action of Therapeutic Anti-Cancer mAbs.Antibodies (Basel, Switzerland) · 2020Review
- Adenovirus vectors in hematopoietic stem cell genome editing.FEBS letters · 2019Review
- The Role of Membrane Bound Complement Regulatory Proteins in Tumor Development and Cancer Immunotherapy.Frontiers in immunology · 2019Review
- Preclinical safety, pharmacokinetics, pharmacodynamics, and biodistribution studies with Ad35K++ protein: a novel rituximab cotherapeutic.Molecular therapy. Methods & clinical development · 2016Article
- Recombinant Ad35 adenoviral proteins as potent modulators of human T cell activation.Immunology · 2014Article
- Protein engineering to target complement evasion in cancer.FEBS letters · 2014Review
- Regulation of complement and modulation of its activity in monoclonal antibody therapy of cancer.mAbs · 2014Review
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
We have developed a technology that depletes the complement regulatory protein (CRP) CD46 from the cell surface, and thereby sensitizes tumor cells to complement-dependent cytotoxicity triggered by therapeutic monoclonal antibodies (mAbs). This technology is based on a small recombinant protein, Ad35K++, which induces the internalization and subsequent degradation of CD46. In preliminary studies, we had demonstrated the utility of the combination of Ad35K++ and several commercially available mAbs such as rituximab, alemtuzumab, and trastuzumab in enhancing cell killing in vitro as well as in vivo in murine xenograft and syngeneic tumor models. We have completed scaled manufacturing of Ad35K++ protein in Escherichia coli for studies in nonhuman primates (NHPs). In macaques, we first defined a dose of the CD20-targeting mAb rituximab that did not deplete CD20-positive peripheral blood cells. Using this dose of rituximab, we then demonstrated that pretreatment with Ad35K++ reconstituted near complete elimination of B cells. Further studies demonstrated that the treatment was well tolerated and safe. These findings in a relevant large animal model provide the rationale for moving this therapy forward into clinical trials in patients with CD20-positive B-cell malignancies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.