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Fully human therapeutic monoclonal antibodies.
Abstract
Monoclonal antibody (mAb) therapy has been facilitated by a number of technologic advances over the past 30 years. Whereas hybridoma development of murine mAbs was requisite for the development of mAbs as drugs, the inherent immunogenicity of rodent sequences in humans has presented obstacles to the clinical application of mAbs. Sensitization to mAb therapeutics poses significant risk to the patient and may blunt the efficacy of these therapies. The advent of chimeric antibodies lessened but did not eliminate the rodent content of mAbs; thus, immunogenicity remained a concern. Further elimination of rodent sequences enabled the production of humanized mAbs, followed by current technology using phage display and, finally, transgenic mice technology, which allows for the generation of fully human therapeutic mAbs. The reduced immunogenicity of this new generation of mAbs is expected to enhance efficacy, safety, and ease of use. In addition to providing replacements for existing mAb drugs, new technologies have greatly facilitated the optimization and modification of mAbs, opening numerous therapeutic avenues.
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“Denosumab and numerous other fully human therapeutic antibodies have been made in transgenic mice, wherein their murine Ig genes have been deleted and replaced with human orthologs (431, 432).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [431]
In the citing paper
“Another potential advantage of a fully human anti-RANKL antibody is the low potential for immune responses (431), a theoretical attribute that has been borne out in clinical trials with denosumab.”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [431]
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Metadata
- Authors
- Weiner, L. M.
- Affiliations
- Fox Chase Cancer Center (US)
- Corresponding author
- Weiner, Louis M
- ORCID
- Weiner, Louis M
- Venue
- Journal of Immunotherapy
- Published
- 2006-01
- Volume
- 29
- Issue
- 1
- Pages
- 1-9
- ISSN
- 1524-9557 (ISSN-L)
- OpenAlex
- W1971456299
- Cited by
- 164
- References
- 36
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 5 · 2019: 7 · 2018: 4 · 2017: 1 · 2016: 5 · 2015: 9 · 2014: 8 · 2013: 9 · 2012: 17
- FWCI
- 2.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Immunotherapy (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA 50633, CA06926, R01CA050633)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
- Keywords
- monoclonal antibodies, fully human antibodies, immunogenicity, chimeric antibodies, humanized monoclonal antibody, transgenic mice, phage display, hybridoma technology, antibody engineering, therapeutic antibodies
- MeSH terms
- Animals, Antibodies, Monoclonal, Genetic Engineering, Humans, Mice, Transgenic, Mice
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