Biophysical Evaluation of Rhesus Macaque Fc Gamma Receptors Reveals Similar IgG Fc Glycoform Preferences to Human Receptors
Rhesus macaques are a common non-human primate model used in the evaluation of human monoclonal antibodies, molecules whose effector functions depend on a conserved N-linked glycan in the Fc region. This carbohydrate is a target of glycoengineering efforts aimed at altering antibody effector functio...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.754710/full |
| _version_ | 1819147086484996096 |
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| author | Andrew R. Crowley Nana Yaw Osei-Owusu Gillian Dekkers Wenda Gao Manfred Wuhrer Diogo M. Magnani Keith A. Reimann Seth H. Pincus Seth H. Pincus Gestur Vidarsson Margaret E. Ackerman Margaret E. Ackerman |
| author_facet | Andrew R. Crowley Nana Yaw Osei-Owusu Gillian Dekkers Wenda Gao Manfred Wuhrer Diogo M. Magnani Keith A. Reimann Seth H. Pincus Seth H. Pincus Gestur Vidarsson Margaret E. Ackerman Margaret E. Ackerman |
| author_sort | Andrew R. Crowley |
| collection | DOAJ |
| description | Rhesus macaques are a common non-human primate model used in the evaluation of human monoclonal antibodies, molecules whose effector functions depend on a conserved N-linked glycan in the Fc region. This carbohydrate is a target of glycoengineering efforts aimed at altering antibody effector function by modulating the affinity of Fcγ receptors. For example, a reduction in the overall core fucose content is one such strategy that can increase antibody-mediated cellular cytotoxicity by increasing Fc-FcγRIIIa affinity. While the position of the Fc glycan is conserved in macaques, differences in the frequency of glycoforms and the use of an alternate monosaccharide in sialylated glycan species add a degree of uncertainty to the testing of glycoengineered human antibodies in rhesus macaques. Using a panel of 16 human IgG1 glycovariants, we measured the affinities of macaque FcγRs for differing glycoforms via surface plasmon resonance. Our results suggest that macaques are a tractable species in which to test the effects of antibody glycoengineering. |
| first_indexed | 2024-12-22T13:24:14Z |
| format | Article |
| id | doaj.art-624dbe4963b94790af2f76bded8b1288 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-22T13:24:14Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-624dbe4963b94790af2f76bded8b12882022-12-21T18:24:23ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-10-011210.3389/fimmu.2021.754710754710Biophysical Evaluation of Rhesus Macaque Fc Gamma Receptors Reveals Similar IgG Fc Glycoform Preferences to Human ReceptorsAndrew R. Crowley0Nana Yaw Osei-Owusu1Gillian Dekkers2Wenda Gao3Manfred Wuhrer4Diogo M. Magnani5Keith A. Reimann6Seth H. Pincus7Seth H. Pincus8Gestur Vidarsson9Margaret E. Ackerman10Margaret E. Ackerman11Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH, United StatesDepartment of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH, United StatesSanquin Research and Landsteiner Laboratory, Academic Medical Centre, Department of Experimental Immunohematology, University of Amsterdam, Amsterdam, NetherlandsAntagen Pharmaceuticals Inc., Boston, MA, United StatesCenter for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, NetherlandsNonhuman Primate Reagent Resource, MassBiologics of the University of Massachusetts Medical School, Boston, MA, United StatesNonhuman Primate Reagent Resource, MassBiologics of the University of Massachusetts Medical School, Boston, MA, United StatesDepartment of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA, United StatesDepartment of Chemistry and Biochemistry, Montana State University, Bozeman, MT, United StatesSanquin Research and Landsteiner Laboratory, Academic Medical Centre, Department of Experimental Immunohematology, University of Amsterdam, Amsterdam, NetherlandsDepartment of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH, United StatesThayer School of Engineering, Dartmouth College, Hanover, NH, United StatesRhesus macaques are a common non-human primate model used in the evaluation of human monoclonal antibodies, molecules whose effector functions depend on a conserved N-linked glycan in the Fc region. This carbohydrate is a target of glycoengineering efforts aimed at altering antibody effector function by modulating the affinity of Fcγ receptors. For example, a reduction in the overall core fucose content is one such strategy that can increase antibody-mediated cellular cytotoxicity by increasing Fc-FcγRIIIa affinity. While the position of the Fc glycan is conserved in macaques, differences in the frequency of glycoforms and the use of an alternate monosaccharide in sialylated glycan species add a degree of uncertainty to the testing of glycoengineered human antibodies in rhesus macaques. Using a panel of 16 human IgG1 glycovariants, we measured the affinities of macaque FcγRs for differing glycoforms via surface plasmon resonance. Our results suggest that macaques are a tractable species in which to test the effects of antibody glycoengineering.https://www.frontiersin.org/articles/10.3389/fimmu.2021.754710/fullnonhuman primateIgGFc gamma receptorN glycanrhesus macaqueADCC - antibody dependent cellular cytotoxicity |
| spellingShingle | Andrew R. Crowley Nana Yaw Osei-Owusu Gillian Dekkers Wenda Gao Manfred Wuhrer Diogo M. Magnani Keith A. Reimann Seth H. Pincus Seth H. Pincus Gestur Vidarsson Margaret E. Ackerman Margaret E. Ackerman Biophysical Evaluation of Rhesus Macaque Fc Gamma Receptors Reveals Similar IgG Fc Glycoform Preferences to Human Receptors Frontiers in Immunology nonhuman primate IgG Fc gamma receptor N glycan rhesus macaque ADCC - antibody dependent cellular cytotoxicity |
| title | Biophysical Evaluation of Rhesus Macaque Fc Gamma Receptors Reveals Similar IgG Fc Glycoform Preferences to Human Receptors |
| title_full | Biophysical Evaluation of Rhesus Macaque Fc Gamma Receptors Reveals Similar IgG Fc Glycoform Preferences to Human Receptors |
| title_fullStr | Biophysical Evaluation of Rhesus Macaque Fc Gamma Receptors Reveals Similar IgG Fc Glycoform Preferences to Human Receptors |
| title_full_unstemmed | Biophysical Evaluation of Rhesus Macaque Fc Gamma Receptors Reveals Similar IgG Fc Glycoform Preferences to Human Receptors |
| title_short | Biophysical Evaluation of Rhesus Macaque Fc Gamma Receptors Reveals Similar IgG Fc Glycoform Preferences to Human Receptors |
| title_sort | biophysical evaluation of rhesus macaque fc gamma receptors reveals similar igg fc glycoform preferences to human receptors |
| topic | nonhuman primate IgG Fc gamma receptor N glycan rhesus macaque ADCC - antibody dependent cellular cytotoxicity |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.754710/full |
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