Immunogenicity of protein therapeutics: The key causes, consequences and challenges

Approaching the asymptote? Evolution and revolution in immunology.Preprint

Janeway, C. (1989) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.1989.054.01.003 · Cited by 3,396 · see citing works

Influence of Immunogenicity on the Long-Term Efficacy of Infliximab in Crohn's Disease

Baert, F., Noman, M., Vermeire, S., Assche, G. V., Haens, G. D., Carbonez, A., & Rutgeerts, P. J. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa020888 · Cited by 2,012 · see citing works

Differential Antigen Processing by Dendritic Cell Subsets in Vivo

Dudziak, D., Kamphorst, A. O., Heidkamp, G. F., Buchholz, V. R., Trumpfheller, C., Yamazaki, S., Cheong, C., Liu, K., Lee, H., Park, C. G., et al. (2007) · Science · doi:10.1126/science.1136080 · Cited by 1,454 · see citing works

Pure Red-Cell Aplasia and Antierythropoietin Antibodies in Patients Treated with Recombinant Erythropoietin

Casadevall, N., Nataf, J., Viron, B. M., Kolta, A. M., Kiladjian, J., Martin-Dupont, P., Michaud, P. A., Papo, T., Ugo, V., Teyssandier, I., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa011931 · Cited by 1,244 · see citing works

F <scp>c</scp> RECEPTOR BIOLOGY

Daëron, M. (1997) · Annual Review of Immunology · doi:10.1146/annurev.immunol.15.1.203 · Cited by 1,227 · see citing works

C3d of complement as a molecular adjuvant: Bridging innate and acquired immunity

Dempsey, P. W., Allison, M. E. D., Akkaraju, S., Goodnow, C. C., & Fearon, D. T. (1996) · Science · doi:10.1126/science.271.5247.348 · Cited by 1,197 · see citing works

Development of a Human Adaptive Immune System in Cord Blood Cell-Transplanted Mice

Traggiai, E., Chicha, L., Mazzucchelli, L., Bronz, L., Piffaretti, J.-C., Lanzavecchia, A., & Manz, M. G. (2004) · Science · doi:10.1126/science.1093933 · Cited by 989 · see citing works

Marginal Zone and B1 B Cells Unite in the Early Response against T-Independent Blood-Borne Particulate Antigens

Martin, F., Oliver, A. M., & Kearney, J. F. (2001) · Immunity · doi:10.1016/s1074-7613(01)00129-7 · Cited by 987 · see citing works

Development of functional human blood and immune systems in NOD/SCID/IL2 receptor γ chainnull mice

Ishikawa, F., Yasukawa, M., Lyons, B. L., Yoshida, S., Miyamoto, T., Yoshimoto, G., Watanabe, T., Akashi, K., Shultz, L. D., & Harada, M. (2005) · Blood · doi:10.1182/blood-2005-02-0516 · Cited by 933 · see citing works

In Vivo Targeting of Antigens to Maturing Dendritic Cells via the DEC-205 Receptor Improves T Cell Vaccination

Bonifaz, L. C., Bonnyay, D., Charalambous, A., Darguste, D. I., Fujii, S., Soares, H., Brimnes, M. K., Moltedo, B., Moran, T. M., & Steinman, R. M. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20032220 · Cited by 921 · see citing works

Spatiotemporal regulation of MyD88–IRF-7 signalling for robust type-I interferon induction

Honda, K., Ohba, Y., Yanai, H., Negishi, H., Mizutani, T., Takaoka, A., Taya, C., & Taniguchi, T. (2005) · Nature · doi:10.1038/nature03547 · Cited by 908 · see citing works

Regulation of dendritic cell numbers and maturation by lipopolysaccharide in vivo.

Smedt, T. D., Pajak, B., Muraille, É., Lespagnard, L., Heinen, E., BAETSELIER, P. D., Urbain, J., Léo, O., & Moser, M. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.184.4.1413 · Cited by 755 · see citing works

The immunogenicity of humanized and fully human antibodies

Harding, F., Stickler, M. M., Razo, J., & DuBridge, R. B. (2010) · mAbs · doi:10.4161/mabs.2.3.11641 · Cited by 743 · see citing works

Several Common HLA-DR Types Share Largely Overlapping Peptide Binding Repertoires

Southwood, S., Sidney, J., Kondo, A., del Guercio, M., Appella, E., Hoffman, S. L., Kubo, R. T., Chesnut, R. W., Grey, H. M., & Sette, A. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.160.7.3363 · Cited by 665 · see citing works

Structure-Immunogenicity Relationships of Therapeutic Proteins

Hermeling, S., Crommelin, D. J. A., Schellekens, H., & Jiskoot, W. (2004) · Pharmaceutical Research · doi:10.1023/b:pham.0000029275.41323.a6 · Cited by 617 · see citing works

Incidence of development of factor VIII and factor IX inhibitors in haemophiliacs

Ehrenforth, S., Kreuz, W., LINDE, R. W. T., Funk, M. B., Güngör, T., Krackhardt, B., Kornhuber, B., & Scharrer, I. (1992) · The Lancet · doi:10.1016/0140-6736(92)90874-3 · Cited by 603 · see citing works

A 13-amino-acid motif in the cytoplasmic domain of FcγRIIB modulates B-cell receptor signalling

Muta, T., Kurosaki, T., Misulovin, Z., Sanchez, M., Nussenzweig, M. C., & Ravetch, J. V. (1994) · Nature · doi:10.1038/368070a0 · Cited by 580 · see citing works

Self- and nonself-recognition by C-type lectins on dendritic cells

Geijtenbeek, T. B. H., van Vliet, S. J., Engering, A., 't Hart, B. A., & van Kooyk, Y. (2004) · Annual Review of Immunology · doi:10.1146/annurev.immunol.22.012703.104558 · Cited by 503 · see citing works

NEUTRALIZING ANTIVIRAL B CELL RESPONSES

Bachmann, M. F., & Zinkernagel, R. M. (1997) · Annual Review of Immunology · doi:10.1146/annurev.immunol.15.1.235 · Cited by 470 · see citing works

B‐cell activation by T‐cell‐independent type 2 antigens as an integral part of the humoral immune response to pathogenic microorganisms

Vos, Q., Lees, A., Wu, Z.-Q., Snapper, C. M., & Mond, J. J. (2000) · Immunological Reviews · doi:10.1034/j.1600-065x.2000.00607.x · Cited by 469 · see citing works

Cytoplasmic Domain Heterogeneity and Functions of IgG Fc Receptors in B Lymphocytes

Amigorena, S., Bonnerot, C., Drake, J. R., Choquet, D., Hunziker, W., Guillet, J., Webster, P. C., Sautès‐Fridman, C., Mellman, I., & Fridman, W. H. (1992) · Science · doi:10.1126/science.1535455 · Cited by 455 · see citing works

Formation of antibodies against infliximab and adalimumab strongly correlates with functional drug levels and clinical responses in rheumatoid arthritis

Radstake, T. R. D. J., Svenson, M., Eijsbouts, A. M. M., van den Hoogen, F. H. J., Enevold, C., van Riel, P. L. C. M., & Bendtzen, K. (2008) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2008.092833 · Cited by 377 · see citing works

Toll-like Receptors Activate Innate and Adaptive Immunity by using Dendritic Cell-Intrinsic and -Extrinsic Mechanisms

Hou, B., Reizis, B., & DeFranco, A. L. (2008) · Immunity · doi:10.1016/j.immuni.2008.05.016 · Cited by 364 · see citing works

Protein Aggregates Seem to Play a Key Role Among the Parameters Influencing the Antigenicity of Interferon Alpha (IFN-α) in Normal and Transgenic Mice

Braun, A. B., Kwee, L., Labow, M., & Alsenz, J. (1997) · Pharmaceutical Research · doi:10.1023/a:1012193326789 · Cited by 299 · see citing works

International workshop on immune tolerance induction: consensus recommendations1

DiMichele, D., Hoots, W. K., PIPE, S. W., et al. (2007) · Haemophilia · doi:10.1111/j.1365-2516.2007.01497.x · Cited by 278 · see citing works

Effective induction of naive and recall T-cell responses by targeting antigen to human dendritic cells via a humanized anti–DC-SIGN antibody

Tacken, P. J., de Vries, I. J. M., Gijzen, K., Joosten, B., Wu, D., Rother, R. P., Faas, S. J., Punt, C. J. A., Torensma, R., Adema, G. J., et al. (2005) · Blood · doi:10.1182/blood-2005-01-0318 · Cited by 271 · see citing works

Anti-infliximab and anti-adalimumab antibodies in relation to response to adalimumab in infliximab switchers and anti-tumour necrosis factor naive patients: a cohort study

Bartelds, G. M., Wijbrandts, C. A., Nurmohamed, M. T., Stapel, S. O., Lems, W. F., Aarden, L. A., Dijkmans, B. A. C., Tak, P. P., & Wolbink, G. (2009) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2009.112847 · Cited by 226 · see citing works

The analysis of the functions of human B and T cells in humanized NOD/shi-scid/γcnull (NOG) mice (hu-HSC NOG mice)

Watanabe, Y., Takahashi, T., Okajima, A., et al. (2009) · International Immunology · doi:10.1093/intimm/dxp050 · Cited by 225 · see citing works

An HLA-DR1 Transgene Confers Susceptibility to Collagen-induced Arthritis Elicited with Human Type II Collagen

Rosloniec, E. F., Brand, D. D., Myers, L. K., Whittington, K. B., Gumanovskaya, M. L., Zaller, D. M., Woods, A., Altmann, D. M., Stuart, J. M., & Kang, A. H. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.185.6.1113 · Cited by 222 · see citing works

Rational design and engineering of therapeutic proteins

Marshall, S. A., Lazar, G. A., Chirino, A. J., & Desjarlais, J. R. (2003) · Drug Discovery Today · doi:10.1016/s1359-6446(03)02610-2 · Cited by 203 · see citing works

Major histocompatibility complex class II polymorphisms in primates

Bontrop, R. E., Otting, Ń., de Groot, N. G., et al. (1999) · Immunological Reviews · doi:10.1111/j.1600-065x.1999.tb01403.x · Cited by 186 · see citing works

Antibody Response to Aggregated Human Interferon Alpha2b in Wild-type and Transgenic Immune Tolerant Mice Depends on Type and Level of Aggregation

Hermeling, S., Schellekens, H., Maas, C., Gebbink, M. F. B. G., Crommelin, D. J. A., & Jiskoot, W. (2006) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.20599 · Cited by 185 · see citing works

Imaging and serum analysis of immune complex formation of radiolabelled infliximab and anti-infliximab in responders and non-responders to therapy for rheumatoid arthritis

van der Laken, C. J., Voskuyl, A. E., Roos, J. C., et al. (2006) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2006.057406 · Cited by 185 · see citing works

Involvement of APO2 ligand/TRAIL in activation-induced death of Jurkat and human peripheral blood T cells

Martínez‐Lorenzo, M. J., Álava, M. A., Gamen, S., Kim, K. J., Chuntharapai, A., Piñeiro, A., Naval, J., & Anel, A. (1998) · European Journal of Immunology · doi:10.1002/(sici)1521-4141(199809)28:09 · Cited by 182 · see citing works

Rationally Engineered Therapeutic Proteins with Reduced Immunogenicity

Tangri, S., Mothé, B. R., Eisenbraun, J., Sidney, J., Southwood, S., Briggs, K., Zinckgraf, J. W., Bilsel, P., Newman, M. J., Chesnut, R. W., et al. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.6.3187 · Cited by 169 · see citing works

HLA-DQ Determines the Response to Exogenous Wheat Proteins: A Model of Gluten Sensitivity in Transgenic Knockout Mice

Black, K. E., Murray, J. A., & David, C. S. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.10.5595 · Cited by 152 · see citing works

Differential effects of three interferon betas on neutralising antibodies in patients with multiple sclerosis: a follow up study in an independent laboratory

Bertolotto, A. (2002) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.73.2.148 · Cited by 145 · see citing works

Phase I Trial of the Prostate-Specific Membrane Antigen–Directed Immunoconjugate MLN2704 in Patients With Progressive Metastatic Castration-Resistant Prostate Cancer

Galsky, M. D., Eisenberger, M., Moore-Cooper, S., Kelly, W. K., Slovin, S. F., DeLaCruz, A., Lee, Y., Webb, I. J., & Scher, H. I. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.15.0532 · Cited by 145 · see citing works

Serological analysis of human anti-human antibody responses in colon cancer patients treated with repeated doses of humanized monoclonal antibody A33.

Ritter, G., Cohen, L., Williams, C., Richards, E. C., Old, L. J., & Welt, S. (2001) · PubMed · Cited by 142 · see citing works

Role of Repetitive Antigen Patterns for Induction of Antibodies Against Antibodies

Fehr, T. H., Bachmann, M. F., Bucher, E. M., et al. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.185.10.1785 · Cited by 137 · see citing works

Radioimmunotherapy of Prostate Cancer Using 90Y- and 177Lu-Labeled J591 Monoclonal Antibodies: Effect of Multiple Treatments on Myelotoxicity

Vallabhajosula, S., Goldsmith, S. J., Kostakoğlu, L., et al. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-1004-0023 · Cited by 129 · see citing works

Distribution of Th1- and Th2-induced Anti-factor VIII IgG Subclasses in Congenital and Acquired Hemophilia Patients

Lei, S., Lei, H., Green, D., et al. (2002) · Thrombosis and Haemostasis · doi:10.1055/s-0037-1613257 · Cited by 125 · see citing works

Pilot Trial of Unlabeled and Indium-111–Labeled Anti–Prostate-Specific Membrane Antigen Antibody J591 for Castrate Metastatic Prostate Cancer

Morris, M. J., Divgi, C. R., Pandit-Taskar, N. D., et al. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-0826 · Cited by 116 · see citing works

Enhancement of IgG anti‐carrier responses by IgG2 anti‐hapten antibodies in mice

Coulie, P. G., & Snick, J. V. (1985) · European Journal of Immunology · doi:10.1002/eji.1830150810 · Cited by 108 · see citing works

Complement activation is required for IgM-mediated enhancement of the antibody response.

Heyman, B., Pilström, L., & Shulman, M. J. (1988) · The Journal of Experimental Medicine · doi:10.1084/jem.167.6.1999 · Cited by 102 · see citing works

Human CD4+ T-cell epitope repertoire on the C2 domain of coagulation factor VIII

Reding, M. T., Okita, D. K., Diethelm-Okita, B. M., Anderson, T. A., & Conti‐Fine, B. M. (2003) · Journal of Thrombosis and Haemostasis · doi:10.1046/j.1538-7836.2003.00251.x · Cited by 99 · see citing works

Clinical link between MHC class II haplotype and interferon-beta (IFN-β) immunogenicity

Barbosa, M. D. F. S., Vielmetter, J., Chu, S. Y., Smith, D. D., & Jacinto, J. M. (2005) · Clinical Immunology · doi:10.1016/j.clim.2005.08.017 · Cited by 99 · see citing works

IgG2a-Mediated Enhancement of Antibody and T Cell Responses and Its Relation to Inhibitory and Activating Fcγ Receptors

Getahun, A., Dahlström, J., Wernersson, S., et al. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.9.5269 · Cited by 94 · see citing works

Sensitization of CD4+ T Cells to Coagulation Factor VIII: Response in Congenital and Acquired Hemophilia Patients and in Healthy Subjects

Reding, M. T., Wu, H., Krampf, M. R., et al. (2000) · Thrombosis and Haemostasis · doi:10.1055/s-0037-1614081 · Cited by 92 · see citing works

Identification and removal of a promiscuous CD4+ T cell epitope from the C1 domain of factor VIII

JONES, T. D., Phillips, W. J., Smith, B. J., BAMFORD, C. A., Nayee, P. D., Baglin, T. P., Gaston, H., & Baker, M. (2005) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2005.01309.x · Cited by 90 · see citing works

Activation of dendritic cells by toll-like receptors and C-type lectins.

Diebold, S. (2009) · Handbook of Experimental Pharmacology · doi:10.1007/978-3-540-71029-5_1 · Cited by 87 · see citing works

Intermolecular cooperativity: a clue to why mice have IgG3?

Greenspan, N. S., & Cooper, L. J. N. (1992) · Immunology Today · doi:10.1016/0167-5699(92)90120-v · Cited by 86 · see citing works

Consequences of immunogenicity to the therapeutic monoclonal antibodies ReoPro and Remicade.

Wagner, C. L., Schantz, A., Barnathan, E. S., et al. (2003) · PubMed · Cited by 85 · see citing works

Antibody Mass Escalation Study in Patients with Castration-Resistant Prostate Cancer Using 111In-J591: Lesion Detectability and Dosimetric Projections for 90Y Radioimmunotherapy

Pandit-Taskar, N. D., O’Donoghue, J. A., Morris, M. J., Wills, E. A., Schwartz, L. H., Gönen, M., Scher, H. I., Larson, S. M., & Divgi, C. R. (2008) · Journal of Nuclear Medicine · doi:10.2967/jnumed.107.049502 · Cited by 83 · see citing works

Elimination of an Immunodominant CD4+ T Cell Epitope in Human IFN-β Does Not Result in an In Vivo Response Directed at the Subdominant Epitope

Yeung, V. P., Chang, J., Miller, J., Barnett, C., Stickler, M. M., & Harding, F. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.11.6658 · Cited by 81 · see citing works

Carbohydrate‐Mediated Targeting of Antigen to Dendritic Cells Leads to Enhanced Presentation of Antigen to T Cells

Adams, E. W., Ratner, D. M., Seeberger, P. H., & Hacohen, N. (2008) · ChemBioChem · doi:10.1002/cbic.200700310 · Cited by 79 · see citing works

Expression and role of Fc- and complement-receptors on human dendritic cells

Bajtay, Z., Csomor, E., Sándor, N., & Erdei, A. (2005) · Immunology Letters · doi:10.1016/j.imlet.2005.11.023 · Cited by 73 · see citing works

FcγRIIB in IgG-Mediated Suppression of Antibody Responses: Different Impact In Vivo and In Vitro

Karlsson, M. C. I., Getahun, A., & Heyman, B. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.10.5558 · Cited by 73 · see citing works

The Immunosuppressive Effect of Passively Administered Antibody IgG Fragments

Cerottini, J., McConahey, P. J., & Dixon, F. J. (1969) · The Journal of Immunology · doi:10.4049/jimmunol.102.4.1008 · Cited by 72 · see citing works

Generation of memory cells. III. Antibody class requirements for the generation of B-memory cells by antigen--antibody complexes.

Gg, K. (1979) · PubMed · Cited by 70 · see citing works

How many specific B cells are needed to protect against a virus?

Bachmann, M. F., Kündig, T. M., Kalberer, C. P., et al. (1994) · The Journal of Immunology · doi:10.4049/jimmunol.152.9.4235 · Cited by 69 · see citing works

A Role for Complement in Feedback Enhancement of Antibody Responses by IgG3

de Ståhl, T. D., Dahlström, J., Carroll, M. C., & Heyman, B. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20022232 · Cited by 69 · see citing works

CD4+ T Cell Response to Factor VIII in Hemophilia A, Acquired Hemophilia, and Healthy Subjects

Reding, M. T., Wu, H., Krampf, M. R., Okita, D. K., Diethelm-Okita, B. M., Key, N. S., & Conti‐Fine, B. M. (1999) · Thrombosis and Haemostasis · doi:10.1055/s-0037-1615873 · Cited by 68 · see citing works

Identification and removal of immunogenicity in therapeutic proteins.

Baker, M., & Jones, T. D. (2007) · PubMed · Cited by 67 · see citing works

Clinical investigation of the immunogenicity of interferon-alpha 2a.

Ryff, J. ‐. (1997) · PubMed · Cited by 67 · see citing works

Epitope repertoire of human CD4 T cells on the A3 domain of coagulation factor VIII

Reding, M. T., Okita, D. K., Diethelm-Okita, B. M., Anderson, T. A., & Conti‐Fine, B. M. (2004) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2004.00850.x · Cited by 64 · see citing works

Antibody Production in Mice Deficient for Complement Receptors 1 and 2 Can Be Induced by IgG/Ag and IgE/Ag, But Not IgM/Ag Complexes

Applequist, S. E., Dahlström, J., Jiang, N., et al. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.5.2398 · Cited by 64 · see citing works

Studies on the Mechanism by Which Antigen‐Specific IgG Suppresses Primary Antibody Responses: Evidence for Epitope Masking and Decreased Localization of Antigen in the Spleen

Getahun, A., & Heyman, B. (2009) · Scandinavian Journal of Immunology · doi:10.1111/j.1365-3083.2009.02298.x · Cited by 62 · see citing works

Immunological aspects of inhibitor development

Reding, M. T. (2006) · Haemophilia · doi:10.1111/j.1365-2516.2006.01363.x · Cited by 62 · see citing works

Serum IFN neutralizing antibodies and neopterin levels in a cross-section of MS patients

Cook, S. D., Quinless, J. R., Jotkowitz, A., Beaton, P., & the Neutralizing Antibody Study Group* (2001) · Neurology · doi:10.1212/wnl.57.6.1080 · Cited by 62 · see citing works

Assessment of the immunogenicity of different interferon beta-1a formulations using ex vivo T-cell assays

Jaber, A., & Baker, M. (2006) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2006.10.023 · Cited by 59 · see citing works

Adalimumab for the treatment of Crohn’s disease

Bianchi-Porro, G., Cassinotti, A., & Ardizzone, S. (2008) · Biologics · doi:10.2147/btt.s3292 · Cited by 58 · see citing works

Biological activity of interferon betas in patients with multiple sclerosis is affected by treatment regimen and neutralising antibodies

Bertolotto, A. (2004) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2004.037259 · Cited by 57 · see citing works

Deimmunization of Monoclonal Antibodies

Jones, T. D., Crompton, L. J., Carr, F. J., et al. (2008) · Methods in molecular biology · doi:10.1007/978-1-59745-554-1_21 · Cited by 56 · see citing works

Neutralizing antibodies to granulocyte–macrophage colony‐stimulating factor, interleukin‐1α and interferon‐α but not other cytokines in human immunoglobulin preparations

Wadhwa, M., Meager, A., Dilger, P., et al. (2000) · Immunology · doi:10.1046/j.1365-2567.2000.00949.x · Cited by 55 · see citing works

T-cell independent IgM and enduring protective IgG antibodies induced by chimeric measles viruses

Fehr, T. H., Naim, H. Y., Bachmann, M. F., et al. (1998) · Nature Medicine · doi:10.1038/nm0898-945 · Cited by 52 · see citing works

New Approaches to Prediction of Immune Responses to Therapeutic Proteins during Preclinical Development

Perry, L., Jones, T. D., & Baker, M. (2008) · Drugs in R&D · doi:10.2165/0126839-200809060-00004 · Cited by 50 · see citing works

Normal immunoglobulin G protects against experimental allergic encephalomyelitis by inducing transferable T cell unresponsiveness to myelin basic protein

Pashov, A. D., Dubey, C., Kaveri, S. V., Lectard, B., Huang, Y., Kazatchkine, M. D., & Bellon, B. (1998) · European Journal of Immunology · doi:10.1002/(sici)1521-4141(199806)28:06 · Cited by 50 · see citing works

The Development of a Modified Human IFN-α2b Linked to the Fc Portion of Human IgG1 as a Novel Potential Therapeutic for the Treatment of Hepatitis C Virus Infection

Jones, T. D., Hanlon, M., Smith, B. J., et al. (2004) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2004.24.560 · Cited by 44 · see citing works

The HLA-DR2 haplotype is associated with an increased proliferative response to the immunodominant CD4+ T-cell epitope in human interferon-β

Stickler, M. M., Valdes, A. M., Gebel, W., et al. (2004) · Genes and Immunity · doi:10.1038/sj.gene.6364027 · Cited by 44 · see citing works

Complement activation is not required for IgG‐mediated suppression of the antibody response

Heyman, B., Wiersma, E. J., & Nose, M. (1988) · European Journal of Immunology · doi:10.1002/eji.1830181113 · Cited by 44 · see citing works

Mucosal antigen presentation and the control of tolerance and immunity

Nagler‐Anderson, C., Terhorst, C., Bhan, A. K., et al. (2001) · Trends in Immunology · doi:10.1016/s1471-4906(00)01830-5 · Cited by 44 · see citing works

Safety and immunogenicity of a new formulation of interferon beta-1a (Rebif (R) new formulation) in a phase IIIb study in patients with relapsing multiple sclerosis: 96-week results

Simsarian, J., Барбараш, О. Л., Casset‐Semanaz, F., et al. (2008) · Cited by 44 · see citing works

Cross-talk between Toll-like receptors 5 and 9 on activation of human immune responses

Merlo, A. C., Calcaterra, C., Ménard, S., & Balsari, A. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0207100 · Cited by 40 · see citing works

Roferon (rIFN-α 2a ) Is More Immunogenic Than Intron A (rIFN-α 2b ) in Patients with Chronic Myelogenous Leukemia

von Wussow, P., Hehlmann, R., Hochhaus, T., Jakschies, D., Nolte, K., Prümmer, O., Ansari, H., Hasford, J., Heimpel, H., & Deicher, H. (1994) · Journal of Interferon Research · doi:10.1089/jir.1994.14.217 · Cited by 38 · see citing works

Induction of immune tolerance by neonatal intravenous injection of human factor VIII in murine hemophilia A

Madoiwa, S., Yamauchi, T., Hakamata, Y., Kobayashi, E., Arai, M., Sugo, T., Mimuro, J., & Sakata, Y. (2004) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7933.2004.00671.x · Cited by 37 · see citing works

The Rebif® New Formulation Story

Jaber, A., Driebergen, R. J., Giovannoni, G., Schellekens, H., Simsarian, J., & Antonelli, M. (2007) · Drugs in R&D · doi:10.2165/00126839-200708060-00002 · Cited by 35 · see citing works

An In Vitro Human Cell-Based Assay to Rank the Relative Immunogenicity of Proteins

Stickler, M. M. (2003) · Toxicological Sciences · doi:10.1093/toxsci/kfh021 · Cited by 24 · see citing works

Induction of factor VIII-specific unresponsiveness by intrathymic factor VIII injection in murine hemophilia A

Madoiwa, S., Yamauchi, T., Kobayashi, E., et al. (2009) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2009.03314.x · Cited by 23 · see citing works

Human population-based identification of CD4+ T-cell peptide epitope determinants

Stickler, M. M., Chin, R., Faravashi, N., et al. (2003) · Journal of Immunological Methods · doi:10.1016/s0022-1759(03)00279-5 · Cited by 17 · see citing works

Induction of Tolerance to Recombinant Therapeutic Proteins

Meritet, J.-F., Maury, C., & Tovey, M. G. (2001) · Journal of Interferon & Cytokine Research · doi:10.1089/107999001317205150 · Cited by 12 · see citing works

The evolution of commercial drug delivery technologies

Vargason, A. M., Anselmo, A. C., & Mitragotri, S. (2021) · Nature Biomedical Engineering · doi:10.1038/s41551-021-00698-w · Cited by 1,361 · see citing works

Design of the Novel Protraction Mechanism of Insulin Degludec, an Ultra-long-Acting Basal Insulin

Jonassen, I., Havelund, S., Hoeg-Jensen, T., Steensgaard, D. B., Wahlund, P.-O., & Ribel, U. (2012) · Pharmaceutical Research · doi:10.1007/s11095-012-0739-z · Cited by 448 · see citing works

Mechanisms of ADC Toxicity and Strategies to Increase ADC Tolerability

Nguyen, T. D., Bordeau, B. M., & Balthasar, J. P. (2023) · Cancers · doi:10.3390/cancers15030713 · Cited by 441 · see citing works

Towards organoid culture without Matrigel

Kozlowski, M. T., Crook, C. J., & Ku, H. T. (2021) · Communications Biology · doi:10.1038/s42003-021-02910-8 · Cited by 409 · see citing works

De novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2

Linsky, T. W., Vergara, R., Codina, N., Nelson, J. W., Walker, M. J., Su, W., Barnes, C. O., Hsiang, T.-Y., Esser-Nobis, K., Yu, K., et al. (2020) · Science · doi:10.1126/science.abe0075 · Cited by 216 · see citing works

Recombinant Human Hyaluronidase-Facilitated Subcutaneous Immunoglobulin Infusion in Primary Immunodeficiency Diseases

Wasserman, R. L. (2017) · Immunotherapy · doi:10.2217/imt-2017-0092 · Cited by 77 · see citing works

Immunogenicity associated with metreleptin treatment in patients with obesity or lipodystrophy

Chan, J. L., Koda, J., Heilig, J. S., Cochran, E. K., Gorden, P., Oral, E. A., & Brown, R. J. (2016) · Clinical Endocrinology · doi:10.1111/cen.12980 · Cited by 72 · see citing works

Translation of angiotensin-converting enzyme 2 upon liver-and lung-targeted delivery of optimized chemically modified mRNA

Schrom, E., Huber, M., Aneja, M., Dohmen, C., Emrich, D., Geiger, J., Hasenpusch, G., Herrmann-Janson, A., Kretzschmann, V., Mykhailyk, O., et al. (2017) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2017.04.006 · Cited by 69 · see citing works

Molecular landscape of anti-drug antibodies reveals the mechanism of the immune response following treatment with TNFα antagonists

Vaisman-Mentesh, A., Rosenstein, S., Yavzori, M., Dror, Y., Fudim, E., Ungar, B., Kopylov, U., Picard, O., Kigel, A., Ben-Horin, S., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02921 · Cited by 54 · see citing works

In vitro models for immunogenicity prediction of therapeutic proteins

Groell, F., Jordan, O., & Borchard, G. (2018) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2018.06.008 · Cited by 53 · 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

Relationship between potential aggregation-prone regions and HLA-DR-binding T-cell immune epitopes: implications for rational design of novel and follow-on therapeutic antibodies

Kumar, S., Mitchell, M. A., Rup, B., & Singh, S. K. (2012) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.23169 · Cited by 33 · see citing works

Immunogenicity of Therapeutic Proteins

Swanson, S. J. (2010) · doi:10.1002/9780470595886.ch4 · Cited by 29 · see citing works

Immunogenicity

Galson, J. D., & O’Connor, D. (2015) · Encyclopedia of Life Sciences · doi:10.1002/9780470015902.a0000937

An overview of scientific and regulatory issues for the immunogenicity of biological products.

Chamberlain, P., & Mire‐Sluis, A. R. (2003) · PubMed · Cited by 31 · see citing works

[An experimental study of the immunogenicity of Pseudomonas aeruginosa vaccines].

Ns, A. (1976) · PubMed

Guidance on Immunogenicity Assessment of Biologically Derived Therapeutic Proteins: A European Perspective

Wadhwa, M., & Thorpe, R. (2011) · doi:10.1002/9781118075685.ch3 · Cited by 4 · see citing works