Analyzing the ‘Degree of Humanness’ of antibody sequences
Abstract
Genetically engineered mouse antibodies are now commonly in clinical use. However, their development is limited because the human immune system tends to regard them as foreign and this triggers an immune response. The solution is to make engineered antibodies appear more human. Here, we propose a method to assess the "degree of humanness" of antibody sequences providing a tool that may contribute to predictions of antigenicity. We analyzed sequences of antibodies belonging to various chains/classes in human and mouse. Our analysis of metrics based on percentage sequence identity between antibody sequences shows distinct differences between human and mouse sequences. Based on mean sequence identity and standard deviation, we calculated Z-scores for data sets of antibody sequences extracted from the Kabat database. We applied the analysis to a set of humanized and chimeric antibodies and to human germline sequences. We conclude that this approach may aid in the selection of more suitable mouse variable domains for antibody engineering to render them more human but in general, we find that typicality of a sequence compared with the expressed human repertoire is not well correlated with antigenicity. We have provided a Web server allowing humanness to be assigned for a sequence.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
There are pharmaceutically focused computational approaches that aid in assessing the immunogenicity and biophysical properties of antibodies.
“There are also pharmaceutically focused computational approaches that aid in assessing the immunogenicity [14] and biophysical properties [15] of antibodies.”
From Computational approaches to therapeutic antibody design: established methods and emerging trends (2020) · cites this paper as [14]
Cites
Improved tools for biological sequence comparison.
Pearson, W. R., & Lipman, D. J. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.8.2444 · Cited by 11,227 · see citing works
SYFPEITHI: database for MHC ligands and peptide motifs
Rammensee, H., Bachmann, J., Emmerich, N., Bachor, O. A., & Stevanović, S. (1999) · Immunogenetics · doi:10.1007/s002510050595 · Cited by 2,316 · see citing works
Humanization of an anti-p185HER2 antibody for human cancer therapy.
Carter, P., Presta, L., Gorman, C., Ridgway, J., Henner, D., Wong, W., Rowland, A., Kotts, C., Carver, M. E., & Shepard, H. (1992) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.89.10.4285 · Cited by 1,958 · see citing works
Reshaping human antibodies for therapy
Riechmann, L., Clark, M., Waldmann, H., & Winter, G. P. (1988) · Nature · doi:10.1038/332323a0 · Cited by 1,562 · see citing works
Replacing the complementarity-determining regions in a human antibody with those from a mouse
Jones, P. T., Dear, P. H., Foote, J., Neuberger, M. S., & Winter, G. (1986) · Nature · doi:10.1038/321522a0 · Cited by 1,406 · see citing works
Making antibodies by phage display technology
Winter, G., Griffiths, A. D., Hawkins, R. E., & Hoogenboom, H. R. (1994) · Annual Review of Immunology · doi:10.1146/annurev.iy.12.040194.002245 · Cited by 1,294 · see citing works
Johnson, S., Oliver, C. N., Prince, G. A., Hemming, V. G., Pfarr, D. S., Wang, S., Dormitzer, M., O'Grady, J., Koenig, S., Tamura, J. K., et al. (1997) · The Journal of Infectious Diseases · doi:10.1086/514115 · Cited by 642 · see citing works
Immunogenicity of engineered antibodies
Hwang, W. Y. K., & Foote, J. (2005) · Methods · doi:10.1016/j.ymeth.2005.01.001 · Cited by 632 · see citing works
A humanized antibody that binds to the interleukin 2 receptor.
Queen, C., Schneider, W. P., Selick, H. E., Payne, P. W., Landolfi, N. F., Duncan, J. F., Avdalovic, N. M., Levitt, M., Junghans, R. P., & Waldmann, T. A. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.24.10029 · Cited by 627 · see citing works
Production of functional chimaeric mouse/human antibody
Boulianne, G. L., Hozumi, N., & Shulman, M. J. (1984) · Nature · doi:10.1038/312643a0 · Cited by 554 · see citing works
Human anti-murine immunoglobulin responses in patients receiving monoclonal antibody therapy.
Schroff, R. W., Foon, K. A., Beatty, S. M., Oldham, R. K., & Morgan, A. C. (1985) · PubMed · Cited by 488 · see citing works
Human immune response to multiple injections of murine monoclonal IgG.
Shawler, D. L., Bartholomew, R. M., Smith, L. M., & Dillman, R. O. (1985) · The Journal of Immunology · doi:10.4049/jimmunol.135.2.1530 · Cited by 423 · see citing works
Mendez, M. J., Green, L. L., Corvalán, J. R. F., Jia, X., Maynard-Currie, C. E., Yang, X.-D., Gallo, M., Louie, D. M., Lee, D. V., Erickson, K. L., et al. (1997) · Nature Genetics · doi:10.1038/ng0297-146 · Cited by 376 · see citing works
Dyer, M. J. S., Hale, G., Hayhoe, F. G. J., & Waldmann, H. (1989) · Blood · doi:10.1182/blood.v73.6.1431.1431 · Cited by 349 · see citing works
Clinical trials of antibody therapy
Glennie, M. J., & Johnson, P. (2000) · Immunology Today · doi:10.1016/s0167-5699(00)01669-8 · Cited by 290 · see citing works
Recombinant antibodies possessing novel effector functions
Neuberger, M. S., Williams, G. T., & Fox, R. O. (1984) · Nature · doi:10.1038/312604a0 · Cited by 282 · see citing works
Antibody humanization: a case of the ‘Emperor’s new clothes’?
Clark, M., & Clark, M. (2000) · Immunology Today · doi:10.1016/s0167-5699(00)01680-7 · Cited by 259 · see citing works
Low, N. M., Holliger, P., & Winter, G. P. (1996) · Journal of Molecular Biology · doi:10.1006/jmbi.1996.0406 · Cited by 216 · see citing works
Humanization of murine monoclonal antibodies through variable domain resurfacing.
Roguska, M., Pedersen, J. T., Keddy, C., Henry, A. H., Searle, S. J., Lambert, J. M., Goldmacher, V. S., Blättler, W. A., Rees, A. R., & Guild, B. C. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.3.969 · Cited by 201 · see citing works
Monoclonal antibodies in the clinic
Reichert, J. M. (2001) · Nature Biotechnology · doi:10.1038/nbt0901-819 · Cited by 169 · see citing works
Vaughan, T. J., Osbourn, J. K., & Tempest, P. R. (1998) · Nature Biotechnology · doi:10.1038/nbt0698-535 · Cited by 159 · see citing works
Use of human germline genes in a CDR homology-based approach to antibody humanization
Hwang, W. Y. K., Almagro, J. C., Buss, T. N., Tan, P., & Foote, J. (2005) · Methods · doi:10.1016/j.ymeth.2005.01.004 · Cited by 97 · see citing works
Kabat database and its applications: Future directions
Johnson, G. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.1.205 · Cited by 93 · see citing works
Human antibody production in transgenic mice: expression from 100 kb of the human IgH locus
Brüggemann, M., Spicer, C., Buluwela, L., Rosewell, I. R., Barton, S. C., Surani, M. A., & Rabbitts, T. H. (1991) · European Journal of Immunology · doi:10.1002/eji.1830210535 · Cited by 80 · see citing works
Humanization of a mouse anti-human IgE antibody: a potential therapeutic for IgE-mediated allergies
Kolbinger, F., Saldanha, J. W., Hardman, N., & Bendig, M. M. (1993) · Protein Engineering Design and Selection · doi:10.1093/protein/6.8.971 · Cited by 71 · see citing works
Humanization of the anti-CEA T84.66 antibody based on crystal structure data
Yazaki, P. J., Sherman, M. A., Shively, J. E., Iklé, D. N., Williams, L. E., Wong, J. Y. C., Colcher, D. M., Wu, A. M., & Raubitschek, A. A. (2004) · Protein Engineering Design and Selection · doi:10.1093/protein/gzh056 · Cited by 71 · see citing works
Advantages of rat monoclonal antibodies
Clark, M., Cobbold, S. P., Hale, G., & Waldmann, H. (1983) · Immunology Today · doi:10.1016/0167-5699(83)90013-0 · Cited by 51 · see citing works
Koh, S. I., Masayuki, T., José, S., Yasuo, K., Ohsugi, Y., Kishimoto, T., & Bendig, M. M. (1994) · Molecular Immunology · doi:10.1016/0161-5890(94)90115-5 · Cited by 46 · see citing works
Can super-antibody drugs be tamed?
(2006) · Nature · doi:10.1038/440855a · Cited by 46 · see citing works
The three-dimensional structure ofEscherichia coliporphobilinogen deaminase at 1.76-Å resolution
Louie, G. V., Brownlie, P. D., Lambert, R., Cooper, J. B., Blundell, T. L., Wood, S., Malashkevich, V. N., Hädener, A., Warren, M. J., & Shoolingin‐Jordan, P. M. (1996) · Proteins Structure Function and Bioinformatics · doi:10.1002/(sici)1097-0134(199605)25:1 · Cited by 43 · see citing works
Self-citationReshaping antibodies for therapy
Routledge, E. G., Gorman, S. D., & Clark, M. (1993) · Cited by 17 · see citing works
Macias, A., Arce, S., Leon, J., Mustelier, G., Bombino, G., Domarco, A., Pérez, R., & Lage, A. (1999) · Hybridoma · doi:10.1089/027245799315925 · Cited by 13 · see citing works
O'Connor, S. J., Meng, Y. G., Rezaie, A. R., & Presta, L. G. (1998) · Protein Engineering Design and Selection · doi:10.1093/protein/11.4.321 · Cited by 13 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Development of therapeutic antibodies for the treatment of diseases
Lu, R., Hwang, Y., Liu, I.-J., Lee, C., Tsai, H.-Z., Li, H., & Wu, H. (2020) · Journal of Biomedical Science · doi:10.1186/s12929-019-0592-z · Cited by 2,106 · see citing works
Antibody Structure and Function: The Basis for Engineering Therapeutics
Chiu, M. L., Goulet, D. R., Teplyakov, A., & Gilliland, G. L. (2019) · Antibodies · doi:10.3390/antib8040055 · Cited by 646 · see citing works
Mason, D. M., Friedensohn, S., Weber, C. R., Jordi, C., Wagner, B., Meng, S. M., Ehling, R. A., Bonati, L., Dahinden, J., Gainza, P., et al. (2021) · Nature Biomedical Engineering · doi:10.1038/s41551-021-00699-9 · Cited by 308 · see citing works
Computer-aided antibody design
Kuroda, D., Shirai, H., Jacobson, M. P., & Nakamura, H. (2012) · Protein Engineering Design and Selection · doi:10.1093/protein/gzs024 · Cited by 222 · see citing works
Computational approaches to therapeutic antibody design: established methods and emerging trends
Norman, R. A., Ambrosetti, F., Bonvin, A. M. J. J., Colwell, L. J., Kelm, S., Kumar, S., & Krawczyk, K. (2020) · Briefings in Bioinformatics · doi:10.1093/bib/bbz095 · Cited by 219 · see citing works
“There are also pharmaceutically focused computational approaches that aid in assessing the immunogenicity [14] and biophysical properties [15] of antibodies.”
BackgroundPrihoda, D., Maamary, J., Waight, A., Juan, V., Fayadat-Dilman, L., Svozil, D., & Bitton, D. A. (2022) · mAbs · doi:10.1080/19420862.2021.2020203 · Cited by 190 · see citing works
abYsis: integrated antibody sequence and structure-management, analysis, and prediction
Swindells, M. B., Porter, C. T., Couch, M., Hurst, J., Abhinandan, K. R., Nielsen, J. H., Macindoe, G., Hetherington, J., & Martin, A. C. R. (2017) · Journal of Molecular Biology · doi:10.1016/j.jmb.2016.08.019 · Cited by 184 · see citing works
Self-citationDevelopment of therapeutic antibodies for the treatment of diseases
Wang, Z., Wang, G., Lu, H., Li, H., Tang, M., & Tong, A. (2022) · Molecular Biomedicine · doi:10.1186/s43556-022-00100-4 · Cited by 136 · see citing works
Lebozec, K., Jandrot‐Perrus, M., Avenard, G., Favre‐Bulle, O., & Billiald, P. (2017) · mAbs · doi:10.1080/19420862.2017.1336592 · Cited by 100 · see citing works
Weitzner, B. D., Kuroda, D., Marze, N. A., Xu, J., & Gray, J. J. (2014) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.24534 · Cited by 94 · see citing works
Monoclonal antibody humanness score and its applications
Gao, S. H., Huang, K., Tu, H., & Adler, A. S. (2013) · BMC Biotechnology · doi:10.1186/1472-6750-13-55 · Cited by 92 · see citing works
Pelat, T., Bedouelle, H., Rees, A. R., Crennell, S. J., Lefranc, M., & Thullier, P. (2008) · Journal of Molecular Biology · doi:10.1016/j.jmb.2008.10.033 · Cited by 91 · see citing works
AbDb: antibody structure database-a database of PDB-derived antibody structures
Ferdous, S., & Martin, A. C. R. (2018) · Database · doi:10.1093/database/bay040 · Cited by 87 · see citing works
Self-citationKhetan, R., Curtis, R., Deane, C. M., Hadsund, J. T., Kar, U., Krawczyk, K., Kuroda, D., Robinson, S. A., Sormanni, P., Tsumoto, K., et al. (2022) · mAbs · doi:10.1080/19420862.2021.2020082 · Cited by 86 · see citing works
Self-citationSzent-Györgyi, C., Stanfield, R. L., Andreko, S. K., Dempsey, A., Ahmed, M., Capek, S., Waggoner, A. S., Wilson, I. A., & Bruchez, M. P. (2013) · Journal of Molecular Biology · doi:10.1016/j.jmb.2013.08.014 · Cited by 84 · see citing works
Li, T., Pantazes, R. J., & Maranas, C. D. (2014) · PLoS ONE · doi:10.1371/journal.pone.0105954 · Cited by 79 · see citing works
Wilman, W., Wróbel, S., Bielska, W., Deszyński, P., Dudzic, P., Jaszczyszyn, I., Kaniewski, J., Młokosiewicz, J., Rouyan, A., Satława, T., et al. (2022) · Briefings in Bioinformatics · doi:10.1093/bib/bbac267 · Cited by 83 · see citing works
Antibody humanization by structure-based computational protein design
Choi, Y., Hua, C. K., Sentman, C. L., Ackerman, M. E., & Bailey‐Kellogg, C. (2015) · mAbs · doi:10.1080/19420862.2015.1076600 · Cited by 77 · see citing works
Rise and Fall of an Anti-MUC1 Specific Antibody
Thie, H., Toleikis, L., Li, J., von Wasielewski, R., Bastert, G., Schirrmann, T., Esteves, I. T., Behrens, C. K., Fournès, B., Fournier, N., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0015921 · Cited by 76 · see citing works
Assessing antibody and nanobody nativeness for hit selection and humanization with AbNatiV
Ramon, A., Ali, M., Atkinson, M., Saturnino, A., Didi, K., Visentin, C., Ricagno, S., Xu, X., Greenig, M., & Sormanni, P. (2024) · Nature Machine Intelligence · doi:10.1038/s42256-023-00778-3 · Cited by 80 · see citing works
How repertoire data are changing antibody science
Marks, C., & Deane, C. M. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.rev120.010181 · Cited by 68 · see citing works
Respaud, R., Marchand, D., Pelat, T., Tchou-Wong, K.-M., Roy, C. J., Parent, C., Cabrera, M., Guillemain, J., MacLoughlin, R. J., Levacher, E., et al. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.05.018 · Cited by 65 · see citing works
Nguyen, A. W., Wagner, E. K., Laber, J. R., Goodfield, L. L., Smallridge, W. E., Harvill, E. T., Papin, J. F., Wolf, R. F., PADLAN, E. A., Bristol, A., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aad0966 · Cited by 61 · see citing works
The INNs and outs of antibody nonproprietary names
Jones, T. D., Carter, P. J., Plückthun, A., Vásquez, M., Holgate, R., Hötzel, I., Popplewell, A. G., Parren, P. W. H. I., Enzelberger, M. M., Rademaker, H. J., et al. (2015) · mAbs · doi:10.1080/19420862.2015.1114320 · Cited by 60 · see citing works
Engineering Venom’s Toxin-Neutralizing Antibody Fragments and Its Therapeutic Potential
Alvarenga, L. M., Zahid, M., Tommaso, A., Juste, M., Aubrey, N., Billiald, P., & Muzard, J. (2014) · Toxins · doi:10.3390/toxins6082541 · Cited by 58 · see citing works
Engineering Stability, Viscosity, and Immunogenicity of Antibodies by Computational Design
Kuroda, D., & Tsumoto, K. (2020) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2020.01.011 · Cited by 58 · see citing works
Apgar, J. R., Mader, M., Agostinelli, R., Benard, S., Bialek, P., Johnson, M., Gao, Y., Krebs, M. R. H., Owens, J. M., Parris, K. D., et al. (2016) · mAbs · doi:10.1080/19420862.2016.1215786 · Cited by 52 · see citing works
Monoclonal antibodies: From magic bullet to precision weapon
Aboul-Ella, H., Gohar, A., Ali, A. A., Ismail, L. M., Mahmoud, A. E. E.-R., Elkhatib, W. F., & Aboul-Ella, H. (2024) · Molecular Biomedicine · doi:10.1186/s43556-024-00210-1 · Cited by 55 · see citing works
Mason, D. M., Friedensohn, S., Weber, C. R., Jordi, C., Wagner, B., Meng, S. M., Gaínza, P., Correia, B. E., & Reddy, S. T. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/617860 · Cited by 50 · see citing works
Humanization of antibodies using a statistical inference approach
Clavero-Álvarez, A., Di Mambro, T., Perez-Gaviro, S., Magnani, M., & Bruscolini, P. (2018) · Scientific Reports · doi:10.1038/s41598-018-32986-y · Cited by 47 · see citing works
Prospects for the computational humanization of antibodies and nanobodies
Gordon, G. L., Raybould, M. I. J., Wong, A., & Deane, C. M. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1399438 · Cited by 47 · see citing works
Machine Learning Attempts for Predicting Human Subcutaneous Bioavailability of Monoclonal Antibodies
Lou, H., & Hageman, M. J. (2021) · Pharmaceutical Research · doi:10.1007/s11095-021-03022-y · Cited by 40 · see citing works
Therapeutic Monoclonal Antibodies: Past, Present, and Future
Strohl, W. R. (2009) · doi:10.1002/9780470485408.ch1 · Cited by 39 · see citing works
The Humanness of Macaque Antibody Sequences
Thullier, P., Huish, O., Pelat, T., & Martin, A. C. R. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2009.12.041 · Cited by 38 · see citing works
Self-citationTabhu: tools for antibody humanization
Olimpieri, P. P., Marcatili, P., & Tramontano, A. L. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu667 · Cited by 38 · see citing works
Yang, Y. X., Wang, P., & Zhu, B. T. (2022) · Journal of Molecular Graphics and Modelling · doi:10.1016/j.jmgm.2022.108364 · Cited by 30 · see citing works
Looking for therapeutic antibodies in next generation sequencing repositories
Krawczyk, K., Raybould, M., Kovaltsuk, A., & Deane, C. M. (2019) · doi:10.1101/572958 · Cited by 29 · see citing works
Burkovitz, A., & Ofran, Y. (2015) · mAbs · doi:10.1080/19420862.2015.1123365 · Cited by 29 · see citing works
Goodchild, S., O'Brien, L., Steven, J., Müller, M. R., Lanning, O. J., Logue, C., D'Elia, R., Phillpotts, R., & Perkins, S. D. (2011) · Antiviral Research · doi:10.1016/j.antiviral.2011.01.010 · Cited by 32 · see citing works
Development of human-like scFv-Fc antibodies neutralizing Botulinum toxin serotype B
Rasetti‐Escargueil, C., Avril, A., Chahboun, S., Tierney, R., Bak, N., Miethe, S., Mazuet, C., Popoff, M. R., Thullier, P., Hust, M., et al. (2015) · mAbs · doi:10.1080/19420862.2015.1082016 · Cited by 27 · see citing works
Antibody affinity maturation by computational design
Kuroda, D., & Tsumoto, K. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-8648-4_2 · Cited by 26 · see citing works
Chahboun, S., Hust, M., Liu, Y., Pelat, T., Miethe, S., Helmsing, S., Jones, R. G. A., Sesardic, D., & Thullier, P. (2011) · BMC Biotechnology · doi:10.1186/1472-6750-11-113 · Cited by 26 · see citing works
Townsend, S., Fennell, B. J., Apgar, J. R., Lambert, M. A., McDonnell, B., Grant, J., Wade, J. M., Franklin, E., Foy, N., Shúilleabháin, D. N., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1510944112 · Cited by 26 · see citing works
How can we discover developable antibody-based biotherapeutics?
Bauer, J., Rajagopal, N., Gupta, P., Gupta, P. K., Nixon, A. E., & Kumar, S. (2023) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2023.1221626 · Cited by 27 · see citing works
Development of scoring functions for antibody sequence assessment and optimization
Seeliger, D. (2013) · PLoS ONE · doi:10.1371/journal.pone.0076909 · Cited by 24 · see citing works
Thullier, P., Chahboun, S., & Pelat, T. (2010) · mAbs · doi:10.4161/mabs.2.5.12545 · Cited by 21 · see citing works
Monovalent TNF receptor 1-selective antibody with improved affinity and neutralizing activity
Richter, F., Zettlitz, K. A., Seifert, O., Herrmann, A., Scheurich, P., Pfizenmaier, K., & Kontermann, R. E. (2018) · mAbs · doi:10.1080/19420862.2018.1524664 · Cited by 20 · see citing works
Edwardraja, S., Rameshkumar, N., Vijayaraj, R., Venkatesan, S., & Lee, S. (2010) · Biotechnology and Bioengineering · doi:10.1002/bit.22702 · Cited by 19 · see citing works
Bispecific antibody targeting both B7-H3 and PD-L1 exhibits superior antitumor activities
Li, H.-Y., Chen, Y., Deng, X., Li, H., Tan, J., Liu, G., Zheng, Y., Pei, M., Peng, K.-T., Yue, L.-L., et al. (2023) · Acta Pharmacologica Sinica · doi:10.1038/s41401-023-01118-2 · Cited by 19 · see citing works
Akbari, B., Farajnia, S., Zarghami, N., Mahdieh, N., Rahmati, M., Khosroshahi, S. A., & Rahbarnia, L. (2016) · Protein Expression and Purification · doi:10.1016/j.pep.2016.06.001 · Cited by 17 · see citing works
Tanner, J. E., Hu, J. S., & Alfieri, C. (2018) · Cancers · doi:10.3390/cancers10040112 · Cited by 15 · see citing works
Selectively targeting disease‐restricted secretogranin III to alleviate choroidal neovascularization
Ji, L., Waduge, P., Hao, L., Kaur, A., Wan, W., Wu, Y. L., Tian, H., Zhang, J., Webster, K. A., & Li, W. (2021) · The FASEB Journal · doi:10.1096/fj.202101085rr · Cited by 15 · see citing works
Lo, K.-M., Léger, O. J. P., & Hock, B. M. (2014) · Microbiology Spectrum · doi:10.1128/microbiolspec.aid-0007-12 · Cited by 15 · see citing works
Loxoscelism: Advances and Challenges in the Design of Antibody Fragments with Therapeutic Potential
Karim-Silva, S., Becker-Finco, A., Jiacomini, I. G., Boursin, F., Leroy, A., Noiray, M., de Moura, J. F., Aubrey, N., Billiald, P., & Alvarenga, L. M. (2020) · Toxins · doi:10.3390/toxins12040256 · Cited by 14 · see citing works
Ros, F., Offner, S., Klostermann, S., Thorey, I. S., Niersbach, H., Breuer, S., Zarnt, G., Lorenz, S. H., Puels, J., Siewe, B. T., et al. (2020) · mAbs · doi:10.1080/19420862.2020.1846900 · Cited by 14 · see citing works
Tiwari, A., Khanna, N., Acharya, S. K., & Sinha, S. (2009) · Vaccine · doi:10.1016/j.vaccine.2009.02.019 · Cited by 14 · see citing works
Reprogramming human B cells with custom heavy-chain antibodies
Rogers, G. L., Huang, C., Mathur, A., Huang, X., Chen, H.-Y., Stanten, K., Morales, H., Chang, C.-H., Kezirian, E. J., & Cannon, P. M. (2024) · Nature Biomedical Engineering · doi:10.1038/s41551-024-01240-4 · Cited by 13 · see citing works
Schmitz, S., Soto, C. S., Crowe, J. E., & Meiler, J. (2020) · mAbs · doi:10.1080/19420862.2020.1758291 · Cited by 12 · see citing works
CAR-T cells targeting CD155 reduce tumor burden in preclinical models of leukemia and solid tumors
Xiong, T.-C., Wang, G., Yu, P., Li, Z., Li, D., Zhang, J., Lu, S., Yang, R., Lian, X., Mi, J., et al. (2025) · Journal of Clinical Investigation · doi:10.1172/jci189920 · Cited by 11 · see citing works
Gallo, E. (2024) · Journal of Biomedical Science · doi:10.1186/s12929-024-01018-5 · Cited by 13 · see citing works
Humanized antibody neutralizing 2009 pandemic H1N1 virus
Shembekar, N., Mallajosyula, V. V. A., Chaudhary, P., Upadhyay, V., Varadarajan, R., & Sk, G. (2014) · Biotechnology Journal · doi:10.1002/biot.201400083 · Cited by 10 · see citing works
Zettlitz, K. A., Seitter, J., Müller, D., & Kontermann, R. E. (2010) · Molecular Biotechnology · doi:10.1007/s12033-010-9298-x · Cited by 10 · see citing works
Amiri, M. M., Golsaz‐Shirazi, F., Soltantoyeh, T., Hosseini, R., Bahadori, T., Khoshnoodi, J., Navabi, S. S., Farid, S., Karimi‐Jafari, M. H., Jeddi‐Tehrani, M., et al. (2017) · Investigational New Drugs · doi:10.1007/s10637-017-0518-0 · Cited by 9 · see citing works
Identifying the Epitope Regions of Therapeutic Antibodies Based on Structure Descriptors
Qiu, J., Qiu, T., Huang, Y., & Cao, Z. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18112457 · Cited by 9 · see citing works
T-SCAPE: T cell immunogenicity scoring via cross-domain aided predictive engine
Kim, J., Jung, N., Lee, J. Y., Cho, N., Noh, J., & Seok, C. (2025) · Science Advances · doi:10.1126/sciadv.adz8759 · Cited by 8 · see citing works
Ahmadzadeh, V., Farajnia, S., Feizi, M. A. H., & Khavari‐Nejad, R. A. (2014) · Protein Expression and Purification · doi:10.1016/j.pep.2014.07.008 · Cited by 8 · see citing works
Ramon, A., Ali, M., Atkinson, M., Saturnino, A., Didi, K., Visentin, C., Ricagno, S., Xu, X., Greenig, M., & Sormanni, P. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.04.28.538712 · Cited by 8 · see citing works
Zhu, Z., Olson, K. S., & Magliery, T. J. (2024) · Antibodies · doi:10.3390/antib13040099 · Cited by 7 · see citing works
A humanized Anti-YKL-40 antibody inhibits tumor development
Yu, H., Wang, Z., Zhu, B., Jia, Z., Luo, J., Xiao, H., Chen, H., & Shao, R. (2024) · Biochemical Pharmacology · doi:10.1016/j.bcp.2024.116335 · Cited by 7 · see citing works
Liu, X., Chen, Y., Liu, G., Deng, X., Cui, Y. J., Tan, J., Dong, X., Li, H., Chen, G., Ou, Z., et al. (2022) · FEBS Open Bio · doi:10.1002/2211-5463.13464 · Cited by 7 · see citing works
Antibody Engineering: Humanization, Affinity Maturation, and Selection Techniques
Almagro, J. C., & Strohl, W. R. (2009) · doi:10.1002/9780470485408.ch13 · Cited by 7 · see citing works
SITA: Predicting site-specific immunogenicity for therapeutic antibodies
Cun, Y., Ding, H., Mao, T., Wang, Y., Wang, C., Li, J., Li, Z., Hu, M., Cao, Z., & Qiu, T. (2025) · Journal of Pharmaceutical Analysis · doi:10.1016/j.jpha.2025.101316 · Cited by 6 · see citing works
Martin, A. C. R., & Rees, A. R. (2016) · Protein Engineering Design and Selection · doi:10.1093/protein/gzw018 · Cited by 6 · see citing works
Self-citationConstruction of Macaque Immune-Libraries
Avril, A., Miethe, S., Hust, M., & Pelat, T. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-7447-4_5 · Cited by 6 · see citing works
Antibody Fragments Humanization: Beginning with the End in Mind
Aubrey, N., & Billiald, P. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-8958-4_10 · Cited by 6 · see citing works
Engineering Antibodies for Cancer Therapy
Goldsmith, L. E., & Robinson, M. K. (2011) · Cell engineering · doi:10.1007/978-94-007-1257-7_10 · Cited by 5 · see citing works
Ramon, A., Frassetto, N., Zhao, H., Xu, X., Greenig, M., Onuoha, S. C., & Sormanni, P. (2026) · mAbs · doi:10.1080/19420862.2026.2646361 · Cited by 5 · see citing works
Sharifi, J., Khirehgesh, M. R., Akbari, B., Soleymani, B., & Mansouri, K. (2021) · Molecular Biotechnology · doi:10.1007/s12033-021-00317-8 · Cited by 4 · see citing works
Yadav, A. J., Bhagat, K., Sharma, A., & Padhi, A. K. (2025) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2024.10.011 · Cited by 3 · see citing works
An adaptive autoregressive diffusion approach to design active humanized antibodies and nanobodies
Ma, J., Wu, F., Xu, T., Xu, S., Liu, W., Yan, L., Qu, M., Yang, X., Bai, Q., Xiao, J., et al. (2025) · Nature Machine Intelligence · doi:10.1038/s42256-025-01120-9 · Cited by 6 · see citing works
Kovalova, N., Boyles, J. S., Wen, Y., Witcher, D. R., Brown‐Augsburger, P., Wroblewski, V. J., & Chlewicki, L. K. (2020) · Biopharmaceutics & Drug Disposition · doi:10.1002/bdd.2222 · Cited by 3 · see citing works
Bioinformatics Tools for Analysis of Antibodies
Martin, A. C. R., & Allen, J. (2014) · doi:10.1002/9783527682423.ch9 · Cited by 3 · see citing works
Self-citationEngineering Antibody‐Based Therapeutics: Progress and Opportunities
Nguyen, A. W., & Maynard, J. A. (2021) · Wiley eBooks · doi:10.1002/9783527815128.ch13 · Cited by 3 · see citing works
An adaptive autoregressive diffusion approach to design active humanized antibody and nanobodyPreprint
Ma, J., Wu, F., Xu, T., Xu, S., Liu, W., Yan, D., Bai, Q., & Yao, J. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.10.22.619416 · Cited by 3 · see citing works
Thongheang, K., Pamonsupornwichit, T., Sornsuwan, K., Juntit, O.-A., Chokepaichitkool, T., Thongkum, W., Yasamut, U., & Tayapiwatana, C. (2025) · Antibodies · doi:10.3390/antib14020036 · Cited by 2 · see citing works
Lo, K.-M., Léger, O. J. P., & Hock, B. M. (2015) · ASM Press eBooks · doi:10.1128/9781555817411.ch19 · Cited by 2 · see citing works
Herding cats: predicting immunogenicity from heterogeneous clinical trials dataPreprint
Dudzic, P., & Krawczyk, K. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.14.682375 · Cited by 2 · see citing works
Stewart, C. A., Shaji, D., Curvino, E. J., Zhang, Y., Kamboh, H., Sergueev, K. V., Ngo-Casi, M., Chowdhury, A., Xu, H., Li, Y., et al. (2025) · Nature Biomedical Engineering · doi:10.1038/s41551-025-01552-z · Cited by 1 · see citing works
HuAbDiffusion: a discrete language diffusion model used for antibody humanization
Liu, D., Hao, X., & Fan, L. (2025) · Briefings in Bioinformatics · doi:10.1093/bib/bbaf658 · Cited by 1 · see citing works
Xu, X., Qiu, S., Wang, Z., Li, D., Chen, M., Chu, Y., Li, G., Fang, Y., Li, C. J., Shi, F., et al. (2026) · Advanced Science · doi:10.1002/advs.202519746 · Cited by 1 · see citing works
Therapeutic Approaches to Employ Monoclonal Antibody for Cancer Treatment
Martins, S., Salvi, P., Lavuri, S. T., Srivastava, M., Sakthivel, S., Barman, M. K., Chand, K., Singh, M., Sonkar, S. C., & Bhukya, P. (2020) · Advances in medical diagnosis, treatment, and care (AMDTC) book series · doi:10.4018/978-1-7998-6530-8.ch002 · Cited by 1 · see citing works
Monoclonal antibodies: recent development in drug delivery
Ashique, S., Guptha, P. M., Kanoujia, J., Garg, A., Hussain, A., Lakshmi, S. M., & Mishra, N. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-91924-1.00014-9 · Cited by 1 · see citing works
Li, S., Wang, Z., Guo, X., & Tang, Y. (2024) · Neoplasia · doi:10.1016/j.neo.2024.101084 · Cited by 1 · see citing works
(2012) · Elsevier eBooks · doi:10.1016/b978-1-907568-37-4.50029-4 · Cited by 1 · see citing works
Sequence and structural analysis of antibodies
Raghavan, A. (2009) · OpenGrey (Institut de l'Information Scientifique et Technique) · Cited by 1 · see citing works
Bauer, J., Kube, S., Gupta, P. K., & Kumar, S. (2024) · Springer eBooks · doi:10.1007/978-3-031-62007-2_14
Szataniak, I., & Packi, K. (2026) · Antibodies · doi:10.3390/antib15050081
Rogers, G. (2026) · Zenodo (CERN European Organization for Nuclear Research) · doi:10.5281/zenodo.19503672
- Authors
- Abhinandan, K. R., & Martin, A. C. R.
- Affiliations
- University College London (GB)
- Corresponding author
- Martin, Andrew C.R.
- ORCID
- Martin, Andrew C.R.
- Venue
- Journal of Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2007-06
- Volume
- 369
- Issue
- 3
- Pages
- 852-862
- ISSN
- 0022-2836 (ISSN-L)
- OpenAlex
- W2037914743
- Cited by
- 99
- References
- 33
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 10 · 2023: 4 · 2022: 7 · 2021: 5 · 2020: 8 · 2019: 4 · 2018: 6 · 2017: 4 · 2016: 5 · 2015: 7 · 2014: 8 · 2013: 3 · 2012: 2
- FWCI
- 2.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- genetically engineered antibodies, humanized monoclonal antibody, chimeric antibodies, sequence identity, variable domains, antigenicity prediction, human-mouse comparison, web server
- MeSH terms
- Animals, Antibodies, Antibodies, Monoclonal, Antibody Specificity, Humans, Immunoglobulin Variable Region, Immunosuppressive Agents, Species Specificity, Protein Engineering, Models, Statistical, Protein Structure, Tertiary, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
