The Galα1,3Galβ1,4GlcNAc-R (α-Gal) epitope: A carbohydrate of unique evolution and clinical relevance
Open accessAbstract
In 1985, we reported that a naturally occurring human antibody (anti-Gal), produced as the most abundant antibody (1% of immunoglobulins) throughout the life of all individuals, recognizes a carbohydrate epitope Galalpha1-3Galbeta1-4GlcNAc-R (the alpha-gal epitope). Since that time, an extensive literature has developed on discoveries related to the alpha-gal epitope and the anti-Gal antibody, including the barrier they form in xenotransplantation and their reciprocity in mammalian evolution. This review covers these topics and new avenues of clinical importance related to this unique antigen/antibody system (alpha-gal epitope/anti-Gal) in improving the efficacy of viral vaccines and in immunotherapy against cancer.
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Murine cells can produce α-gal and Neu5Gc at considerably higher levels than hamster cells, increasing the risks of immunogenicity.
“Murine cells can also produce α-gal and Neu5Gc at considerably higher levels than hamster cells, increasing the risks of immunogenicity (Tangvoranuntakul et al., 2003;Chung et al., 2008;Macher and Galili, 2008;Padler-Karavani et al., 2008;Ghaderi et al., 2012).”
From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Macher and Galili, 2008
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Cetuximab-Induced Anaphylaxis and IgE Specific for Galactose-α-1,3-Galactose
Chung, C. H., Mirakhur, B., Chan, E., Le, Q.-T., Berlin, J., Morse, M., Murphy, B. A., Satinover, S. M., Hosen, J., Mauro, D., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa074943 · Cited by 1,521 · see citing works
The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line
Xu, X., Nagarajan, H., Lewis, N. E., Pan, S., Cai, Z., Liu, X., Chen, W., Xie, M., Wang, W., Hammond, S., et al. (2011) · Nature Biotechnology · doi:10.1038/nbt.1932 · Cited by 785 · see citing works
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“Humans and higher primates do not have a functional gene encoding the transferase that adds galactose in α(1–3) linkage; however, owing to continual environmental exposure, humans have an IgG antibody that is specific for this antige”
BackgroundLiu, L. (2015) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.24444 · Cited by 428 · see citing works
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The Possible Role of Anti-Neu5Gc as an Obstacle in Xenotransplantation
Tector, A. J., Mosser, M., Tector, M., & Bach, J.-M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00622 · Cited by 60 · see citing works
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Quantification of α-Gal Antigen Removal in the Porcine Dermal Tissue by α-Galactosidase
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- Authors
- Macher, B. A., & Galili, U.
- Affiliations
- San Francisco State University (US)
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Macher, Bruce A.
- ORCID
- Galili, Uri
- Venue
- Biochimica et Biophysica Acta (BBA) - General Subjects
- Publisher
- Elsevier BV
- Published
- 2008-02
- Volume
- 1780
- Issue
- 2
- Pages
- 75-88
- ISSN
- 0304-4165 (ISSN-L)
- PMC
- PMC2271034
- OpenAlex
- W2073529249
- Cited by
- 404
- References
- 1
- Citations by year
- 2026: 11 · 2025: 17 · 2024: 25 · 2023: 13 · 2022: 12 · 2021: 33 · 2020: 30 · 2019: 22 · 2018: 17 · 2017: 20 · 2016: 15 · 2015: 23 · 2014: 26 · 2013: 26 · 2012: 39
- FWCI
- 2.57
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - General Subjects (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM040205)
- National Institute of Allergy and Infectious Diseases (R21AI58749)
- National Institutes of Health
- National Cancer Institute (R01CA85868)
- Topics
- Health Sciences › Medicine › Surgery › Xenotransplantation and immune response
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Health Sciences › Medicine › Hematology › Blood groups and transfusion
- Keywords
- alpha-gal epitope, anti-Gal antibodies, carbohydrate antigens, xenotransplantation, xenotransplantation barriers, mammalian evolution, cancer immunotherapy
- MeSH terms
- Animals, Galactosyltransferases, Humans, Immunoglobulin G, Substrate Specificity, Transplantation, Heterologous, Trisaccharides, Viral Vaccines, Evolution, Molecular, Cancer Vaccines
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