In vivo anti-tumor efficacy of afucosylated anti-CS1 monoclonal antibody produced in glycoengineered Pichia pastoris
Abstract
Monoclonal antibody (mAb) therapy has been successfully used for the treatment of B-cell lymphomas and is currently extended for the treatment of multiple myeloma (MM). New developments in MM therapeutics have achieved significant survival gains in patients but the disease still remains incurable. Elotuzumab (HuLuc63), an anti-CS1 monoclonal IgG1 antibody, is believed to induce anti-tumor activity and MM cytotoxicity through antibody dependent cellular cytotoxicity (ADCC) and inhibition of MM cell adhesion to bone marrow stromal cells (BMSCs). Modulations of the Fc glycan composition at the N297 site by selective mutations or afucosylation have been explored as strategies to develop bio-better therapeutics with enhanced ADCC activity. Afucosylated therapeutic antibodies with enhanced ADCC activity have been reported to possess greater efficacy in tumor growth inhibition at lower doses when compared to fucosylated therapeutic antibodies. The N-linked glycosylation pathway in Pichia pastoris has been engineered to produce human-like N-linked glycosylation with uniform afucosylated complex type glycans. The purpose of this study was to compare afucosylated anti-CS1 mAb expressed in glycoengineered Pichia pastoris with fucosylated anti-CS1 mAb expressed in mammalian HEK293 cells through in vitro ADCC and in vivo tumor inhibition models. Our results indicate that Fc glycosylation is critical for in vivo efficacy and afucosylated anti-CS1 mAb expressed in glycoengineered Pichia pas…
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The anti-CS1 antibody produced with these cells is afucosylated and has enhanced in vitro ADCC activity and in vivo anti-tumor activity compared to the same antibody produced in HEK293 cells.
“Consequently, the anti-CS1 antibody produced with these cells is afucosylated and has enhanced in vitro ADCC activity and in vivo anti-tumor activity compared to the same antibody produced in HEK293 cells (Gomathinayagam et al., 2015).”
From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Gomathinayagam et al., 2015
Cites
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Dujardin, S., Commins, C., Lathuiliere, A., Beerepoot, P., Fernandes, A. R., Kamath, T. V., De Los Santos, M. B., Klickstein, N., Corjuc, D. L., Corjuc, B. T., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0938-9 · Cited by 438 · see citing works
Self-citationTherapeutic glycoprotein production in mammalian cells
Lalonde, M.-E., & Durocher, Y. (2017) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2017.04.028 · Cited by 296 · see citing works
- Authors
- Gomathinayagam, S., Laface, D., Houston-Cummings, N. R., Mangadu, R., Moore, R., Shandil, I., Sharkey, N., Li, H., Stadheim, T. A., & Zha, D.
- Affiliations
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Corresponding author
- Zha, Dongxing
- Venue
- Journal of Biotechnology
- Publisher
- Elsevier BV
- Published
- 2015-08
- Volume
- 208
- Pages
- 13-21
- ISSN
- 0168-1656 (ISSN-L)
- OpenAlex
- W327289427
- Cited by
- 9
- References
- 2
- Citations by year
- 2026: 1 · 2025: 2 · 2021: 1 · 2020: 1 · 2018: 1 · 2017: 3
- FWCI
- 1.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
- Keywords
- elotuzumab, multiple myeloma, Fc glycosylation, antibody-dependent cellular cytotoxicity, N-glycosylation, tumor growth inhibition, recombinant antibody production
- MeSH terms
- Animals, Antibodies, Monoclonal, Antibodies, Neoplasm, Glycosylation, Humans, Multiple Myeloma, Neoplasms, Experimental, Pichia, Recombinant Proteins, Mice, SCID, Xenograft Model Antitumor Assays, Cell Line, Tumor, HEK293 Cells, Cell Engineering
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