Anti-PEG antibodies: Properties, formation, testing and role in adverse immune reactions to PEGylated nano-biopharmaceuticals
Open accessAbstract
Conjugation of polyethylene glycols (PEGs) to proteins or drug delivery nanosystems is a widely accepted method to increase the therapeutic index of complex nano-biopharmaceuticals. Nevertheless, these drugs and agents are often immunogenic, triggering the rise of anti-drug antibodies (ADAs). Among these ADAs, anti-PEG IgG and IgM were shown to account for efficacy loss due to accelerated blood clearance of the drug (ABC phenomenon) and hypersensitivity reactions (HSRs) entailing severe allergic symptoms with occasionally fatal anaphylaxis. In addition to recapitulating the basic information on PEG and its applications, this review expands on the physicochemical factors influencing its immunogenicity, the prevalence, features, mechanism of formation and detection of anti-PEG IgG and IgM and the mechanisms by which these antibodies (Abs) induce ABC and HSRs. In particular, we highlight the in vitro, animal and human data attesting to anti-PEG Ab-induced complement (C) activation as common underlying cause of both adverse effects. A main message is that correct measurement of anti-PEG Abs and individual proneness for C activation might predict the rise of adverse immune reactions to PEGylated drugs and thereby increase their efficacy and safety.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
In preclinical studies, the presence of anti-PEG IgM in animal serum accelerated nanoparticle clearance.
“In preclinical studies, the presence of anti-PEG IgM in animal serum accelerated nanoparticle clearance and caused a complete loss of the efficacy of mRNA therapeutics217,218.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [218]
In preclinical studies, the presence of anti-PEG IgM in animal serum caused a complete loss of the efficacy of mRNA therapeutics.
“In preclinical studies, the presence of anti-PEG IgM in animal serum accelerated nanoparticle clearance and caused a complete loss of the efficacy of mRNA therapeutics217,218.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [218]
Anti-PEG antibodies might heighten the risk of allergic reactions in certain individuals and impede vaccine efficacy.
“Anti-PEG antibodies have been reported in 40% of the population, which might heighten the risk of allergic reactions in certain individuals and impede vaccine efficacy218.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [218]
Anti-PEG antibodies have been reported in 40% of the population.
“Anti-PEG antibodies have been reported in 40% of the population, which might heighten the risk of allergic reactions in certain individuals and impede vaccine efficacy218.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [218]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Doxil® — The first FDA-approved nano-drug: Lessons learned
Barenholz, Y. (. (2012) · Journal of Controlled Release · doi:10.1016/j.jconrel.2012.03.020 · Cited by 4,792 · see citing works
PEGylation as a strategy for improving nanoparticle-based drug and gene delivery
Suk, J. S., Xu, Q., Kim, N., Hanes, J., & Ensign, L. M. (2016) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2015.09.012 · Cited by 4,523 · see citing works
The controlled intravenous delivery of drugs using PEG-coated sterically stabilized nanospheres
Gref, R., Domb, A. J., Quellec, P., Blunk, T., Müller, R. H., Verbavatz, J., & Langer, R. (1995) · Advanced Drug Delivery Reviews · doi:10.1016/0169-409x(95)00026-4 · Cited by 820 · see citing works
Turecek, P. L., Bossard, M. J., Schoetens, F., & Ivens, I. A. (2016) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2015.11.015 · Cited by 733 · see citing works
The accelerated blood clearance (ABC) phenomenon: Clinical challenge and approaches to manage
Abu Lila, A. S., Kiwada, H., & Ishida, T. (2013) · Journal of Controlled Release · doi:10.1016/j.jconrel.2013.07.026 · Cited by 721 · see citing works
Self-citationArmstrong, J. K., Hempel, G., Koling, S., Chan, L. S., Fisher, T., Meiselman, H. J., & Garratty, G. (2007) · Cancer · doi:10.1002/cncr.22739 · Cited by 699 · see citing works
Hoang Thi, T. T., Pilkington, E. H., Nguyen, D. H., Lee, J. S., Park, K. D., & Truong, N. P. (2020) · Polymers · doi:10.3390/polym12020298 · Cited by 668 · see citing works
Shankar, G., Devanarayan, V., Amaravadi, L. S., Barrett, Y. C., Bowsher, R. R., Finco‐Kent, D., Fiscella, M., Gorovits, B., Kirschner, S., Moxness, M. S., et al. (2008) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2008.09.020 · Cited by 616 · see citing works
Complement activation-related pseudoallergy: A new class of drug-induced acute immune toxicity
Szebeni, J. (2005) · Toxicology · doi:10.1016/j.tox.2005.07.023 · Cited by 610 · see citing works
Self-citationDams, E. T. M., Laverman, P., Oyen, W. J. G., Storm, G., Scherphof, G. L., van der Meer, J. W. M., Corstens, F. H. M., & Boerman, O. C. (2000) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)35391-1 · Cited by 606 · see citing works
Anti‐ <scp>PEG</scp> immunity: emergence, characteristics, and unaddressed questions
Yang, Q., & Lai, S. K. (2015) · WIREs Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1339 · Cited by 593 · see citing works
Validation of immunoassays for bioanalysis: a pharmaceutical industry perspective
Findlay, J. W. A., Smith, W., Lee, J. W., Nordblom, G. D., Das, I., Desilva, B. S., Khan, M. N., & Bowsher, R. R. (2000) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/s0731-7085(99)00244-7 · Cited by 590 · see citing works
Garay, R. P., El-Gewely, R., Armstrong, J. K., Garratty, G., & Richette, P. (2012) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2012.720969 · Cited by 587 · see citing works
PEGylated antibodies and antibody fragments for improved therapy: a review
Chapman, A. P. (2002) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(02)00026-1 · Cited by 558 · see citing works
Ishida, T., Ichihara, M., Wang, X., Yamamoto, K., Kimura, J., Majima, E., & Kiwada, H. (2006) · Journal of Controlled Release · doi:10.1016/j.jconrel.2006.01.005 · Cited by 558 · see citing works
Self-citationPEGylated liposomes: immunological responses
Sayed, M. M. E., Lila, A. S. A., Shimizu, T., Alaaeldin, E., Hussein, A. K., Sarhan, H. A., Szebeni, J., & Ishida, T. (2019) · Science and Technology of Advanced Materials · doi:10.1080/14686996.2019.1627174 · Cited by 536 · see citing works
Self-citationAccelerated blood clearance (ABC) phenomenon upon repeated injection of PEGylated liposomes
Ishida, T., & Kiwada, H. (2007) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2007.11.005 · Cited by 496 · see citing works
Self-citationThe Incidence and Management of Infusion Reactions To Infliximab: A Large Center Experience
Cheifetz, A. S., Smedley, M. V., Martin, S., Reiter, M., Leone, G., Mayer, L., & Plevy, S. E. (2003) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2003.07457.x · Cited by 491 · see citing works
Management and Preparedness for Infusion and Hypersensitivity Reactions
Lenz, H.-J. (2007) · The Oncologist · doi:10.1634/theoncologist.12-5-601 · Cited by 479 · see citing works
Szebeni, J. (2014) · Molecular Immunology · doi:10.1016/j.molimm.2014.06.038 · Cited by 457 · see citing works
Self-citationWang, X., Ishida, T., & Kiwada, H. (2007) · Journal of Controlled Release · doi:10.1016/j.jconrel.2007.02.010 · Cited by 421 · see citing works
Self-citationPEGylated liposomes elicit an anti-PEG IgM response in a T cell-independent manner
Ishida, T., Wang, X., Shimizu, T., Nawata, K., & Kiwada, H. (2007) · Journal of Controlled Release · doi:10.1016/j.jconrel.2007.05.015 · Cited by 382 · see citing works
Self-citationAccelerated clearance of PEGylated liposomes in rats after repeated injections
Ishida, T., Maeda, R., Ichihara, M., Irimura, K., & Kiwada, H. (2003) · Journal of Controlled Release · doi:10.1016/s0168-3659(02)00462-5 · Cited by 327 · see citing works
Self-citationIshida, T., Atobe, K., Wang, X., & Kiwada, H. (2006) · Journal of Controlled Release · doi:10.1016/j.jconrel.2006.08.017 · Cited by 290 · see citing works
Self-citationRichter, A. W., & Akerblom, E. B. (2009) · International Archives of Allergy and Applied Immunology · doi:10.1159/000233309 · Cited by 282 · see citing works
Ganson, N. J., Povsic, T. J., Sullenger, B. A., Alexander, J. H., Zelenkofske, S. L., Sailstad, J. M., Rusconi, C. P., & Hershfield, M. S. (2015) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2015.10.034 · Cited by 275 · see citing works
Ishida, T., Ichihara, M., Wang, X., & Kiwada, H. (2006) · Journal of Controlled Release · doi:10.1016/j.jconrel.2006.08.001 · Cited by 270 · see citing works
Self-citationHershfield, M. S., Ganson, N. J., Kelly, S. J., Scarlett, E., Jaggers, D. A., & Sundy, J. S. (2014) · Arthritis Research & Therapy · doi:10.1186/ar4500 · Cited by 265 · see citing works
Hamad, I. M., Hunter, A. C., Szebeni, J., & Moghimi, S. M. (2008) · Molecular Immunology · doi:10.1016/j.molimm.2008.08.276 · Cited by 253 · see citing works
Self-citationChen, B., Su, Y.-C., Chang, C.-J., Burnouf, P., Chuang, K., Chen, C.-H., Cheng, T., Chen, Y.-T., Wu, J.-Y., & Roffler, S. R. (2016) · Analytical Chemistry · doi:10.1021/acs.analchem.6b03109 · Cited by 241 · see citing works
Richter, A. W., & Akerblom, E. B. (2009) · International Archives of Allergy and Applied Immunology · doi:10.1159/000233512 · Cited by 229 · see citing works
Hussain, Z., Khan, S., Imran, M., Sohail, M. F., Shah, S. W. A., & de Matas, M. (2019) · Drug Delivery and Translational Research · doi:10.1007/s13346-019-00631-4 · Cited by 221 · see citing works
Sundy, J. S., Ganson, N. J., Kelly, S. J., Scarlett, E., Rehrig, C. D., Huang, W. J.-S., & Hershfield, M. S. (2007) · Arthritis & Rheumatism · doi:10.1002/art.22403 · Cited by 219 · see citing works
Kozma, G. T., Mészáros, T., Vashegyi, I., Fülöp, T., Őrfi, E., Dézsi, L., Rosivall, L., Bavli, Y., Urbanics, R., Mollnes, T. E., et al. (2019) · ACS Nano · doi:10.1021/acsnano.9b03942 · Cited by 216 · see citing works
Self-citationMima, Y., Hashimoto, Y., Shimizu, T., Kiwada, H., & Ishida, T. (2015) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.5b00144 · Cited by 213 · see citing works
Self-citationVogel, W. H. (2010) · Clinical journal of oncology nursing · doi:10.1188/10.cjon.e10-e21 · Cited by 204 · see citing works
Povsic, T. J., Lawrence, M. G., Lincoff, A. M., Mehran, R., Rusconi, C. P., Zelenkofske, S. L., Huang, Z., Sailstad, J. M., Armstrong, P. W., Steg, P. G., et al. (2016) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2016.04.058 · Cited by 198 · see citing works
Role of the methoxy group in immune responses to mPEG-protein conjugates
Sherman, M. R., Williams, L. D., Sobczyk, M. A., Michaels, S. J., & Saifer, M. G. P. (2012) · Bioconjugate Chemistry · doi:10.1021/bc200551b · Cited by 185 · see citing works
Sundy, J. S., Becker, M. A., Baraf, H. S. B., Barkhuizen, A., Moreland, L. W., Huang, W. J.-S., Waltrip, R. W., Maroli, A. N., Horowitz, Z., & Pegloticase Phase 2 Study Investigators (2008) · Arthritis & Rheumatism · doi:10.1002/art.23810 · Cited by 177 · see citing works
Hemodynamic Changes Induced by Liposomes and Liposome-Encapsulated Hemoglobin in Pigs
Szebeni, J., Fontana, J. L., Wassef, N. M., et al. (1999) · Circulation · doi:10.1161/01.cir.99.17.2302 · Cited by 176 · see citing works
Self-citationProtein PEGylation for cancer therapy: bench to bedside
Gupta, V. G., Bhavanasi, S., Quadir, M., Singh, K., Ghosh, G., Vasamreddy, K., Ghosh, A., Siahaan, T. J., Banerjee, S., & Banerjee, S. K. (2018) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-018-0492-0 · Cited by 161 · see citing works
Anti-PEG IgM Response against PEGylated Liposomes in Mice and Rats
Ichihara, M., Shimizu, T., Imoto, A., Hashiguchi, Y., Uehara, Y., Ishida, T., & Kiwada, H. (2010) · Pharmaceutics · doi:10.3390/pharmaceutics3010001 · Cited by 157 · see citing works
Self-citationFrancis, G. E. (1998) · International Journal of Hematology · doi:10.1016/s0925-5710(98)00039-5 · Cited by 150 · see citing works
Koide, H., Asai, T., Hatanaka, K., Akai, S., Ishii, T., Kenjo, E., Ishida, T., Kiwada, H., Tsukada, H., & Oku, N. (2010) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2010.03.022 · Cited by 143 · see citing works
Self-citationShiraishi, K., Hamano, M., Ma, H., Kawano, K., Maitani, Y., Aoshi, T., Ishii, K. J., & Yokoyama, M. (2013) · Journal of Controlled Release · doi:10.1016/j.jconrel.2012.11.016 · Cited by 141 · see citing works
Grenier, P., Viana, I. M. D. O., Lima, E. M., & Bertrand, N. (2018) · Journal of Controlled Release · doi:10.1016/j.jconrel.2018.08.022 · Cited by 130 · see citing works
Suzuki, T., Ichihara, M., Hyodo, K., Yamamoto, E., Ishida, T., Kiwada, H., Ishihara, H., & Kikuchi, H. (2012) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2012.07.049 · Cited by 127 · see citing works
Self-citationChen, E., Chen, B., Su, Y.-C., Chang, Y., Cheng, T., Barenholz, Y., & Roffler, S. R. (2020) · ACS Nano · doi:10.1021/acsnano.9b07218 · Cited by 126 · see citing works
Understanding the Role of Anti-PEG Antibodies in the Complement Activation by Doxil in Vitro
Neun, B. W., Barenholz, Y., Szebeni, J., & Dobrovolskaia, M. A. (2018) · Molecules · doi:10.3390/molecules23071700 · Cited by 120 · see citing works
Self-citationRepeated injections of PEG-PE liposomes generate anti-PEG antibodies.
Środa-Pomianek, K., Rydlewski, J., Langner, M., Kozubek, A., Grzybek, M., & Sikorski, A. F. (2005) · PubMed · Cited by 116 · see citing works
Ishida, T., Ichikawa, T., Ichihara, M., et al. (2004) · Journal of Controlled Release · doi:10.1016/j.jconrel.2003.12.011 · Cited by 116 · see citing works
Self-citationXiao, R., Wang, R., Zeng, Z., et al. (2012) · International Journal of Nanomedicine · doi:10.2147/ijn.s34489 · Cited by 112 · see citing works
Saifer, M. G. P., Williams, L. D., Sobczyk, M. A., Michaels, S. J., & Sherman, M. R. (2013) · Molecular Immunology · doi:10.1016/j.molimm.2013.07.014 · Cited by 112 · see citing works
Povsic, T. J., Vavalle, J. P., Aberle, L. H., Kasprzak, J. D., Cohen, M. G., Mehran, R., Bode, C., Buller, C. E. H., Montalescot, G., Cornel, J. H., et al. (2012) · European Heart Journal · doi:10.1093/eurheartj/ehs232 · Cited by 110 · see citing works
Shimizu, T., Ichihara, M., Yoshioka, Y., Ishida, T., Nakagawa, S., & Kiwada, H. (2012) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b12-00276 · Cited by 96 · see citing works
Self-citationCellular Camouflage: Fooling the Immune System with Polymers
Scott, M. D., & Murad, K. L. (1998) · Current Pharmaceutical Design · doi:10.2174/138161280406221011110509 · Cited by 94 · see citing works
Pegylation and Its Impact on the Design of New Protein-Based Medicines
Ginn, C., Khalili, H., Lever, R., & Brocchini, S. (2014) · Future Medicinal Chemistry · doi:10.4155/fmc.14.125 · Cited by 93 · see citing works
Su, Y.-C., Chen, B., Chuang, K.-H., Cheng, T., & Roffler, S. R. (2010) · Bioconjugate Chemistry · doi:10.1021/bc100067t · Cited by 93 · see citing works
McCool, T. L., Harding, C. V., Greenspan, N. S., & Schreiber, J. R. (1999) · Infection and Immunity · doi:10.1128/iai.67.9.4862-4869.1999 · Cited by 89 · see citing works
Shimizu, T., Mima, Y., Hashimoto, Y., Ukawa, M., Ando, H., Kiwada, H., & Ishida, T. (2015) · Immunobiology · doi:10.1016/j.imbio.2015.06.005 · Cited by 86 · see citing works
Self-citationShimizu, T., Ishida, T., & Kiwada, H. (2012) · Immunobiology · doi:10.1016/j.imbio.2012.08.274 · Cited by 85 · see citing works
Self-citationWang, X., Ishida, T., Ichihara, M., et al. (2005) · Journal of Controlled Release · doi:10.1016/j.jconrel.2005.01.008 · Cited by 84 · see citing works
Self-citationPolyethylene glycol in spinal cord injury repair: a critical review
Lu, X., Perera, T. H., Aria, A. B., & Callahan, L. A. S. (2018) · Journal of Experimental Pharmacology · doi:10.2147/jep.s148944 · Cited by 83 · see citing works
Gabizón, A., & Szebeni, J. (2020) · ACS Nano · doi:10.1021/acsnano.0c03648 · Cited by 82 · see citing works
Self-citationArmstrong, J. K. (2009) · Birkhäuser Basel eBooks · doi:10.1007/978-3-7643-8679-5_9 · Cited by 81 · see citing works
PEG‐asparaginase allergy in children with acute lymphoblastic leukemia in the NOPHO ALL2008 protocol
Henriksen, L. T., Harila‐Saari, A. H., Ruud, E., Abrahamsson, J., Pruunsild, K., Vaitkevičienė, G. E., Jónsson, Ó. G., Schmiegelow, K., Heyman, M. M., Schrøder, H. D., et al. (2014) · Pediatric Blood & Cancer · doi:10.1002/pbc.25319 · Cited by 80 · see citing works
Suzuki, T., Ichihara, M., Hyodo, K., Yamamoto, E., Ishida, T., Kiwada, H., Kikuchi, H., & Ishihara, H. (2014) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2014.09.047 · Cited by 74 · see citing works
Self-citationValidation of immunoassays used to assess immunogenicity to therapeutic monoclonal antibodies
Geng, D., Shankar, G., Schantz, A., Rajadhyaksha, M., Davis, H. M., & Wagner, C. L. (2005) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2005.04.045 · Cited by 71 · see citing works
The early days of PEG and PEGylation (1970s–1990s)
Hoffman, A. S. (2016) · Acta Biomaterialia · doi:10.1016/j.actbio.2016.05.029 · Cited by 68 · see citing works
Liu, Y., Reidler, H., Pan, J., Milunic, D., Qin, D., Chen, D., Vallejo, R. P., & Yin, R. (2011) · Journal of Pharmacological and Toxicological Methods · doi:10.1016/j.vascn.2011.07.003 · Cited by 64 · see citing works
Xu, H., Ye, F., Hu, M., Yin, P., Zhang, W., Li, Y., Xiu, Y., & Deng, Y. (2014) · Drug Delivery · doi:10.3109/10717544.2014.885998 · Cited by 64 · see citing works
Chang, C.-J., Chen, C.-H., Chen, B., Su, Y.-C., Chen, Y., Hershfield, M. S., Lee, M. M., Chen, Y.-T., Chen, Y.-T., Roffler, S. R., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00622-4 · Cited by 64 · see citing works
Hashimoto, Y., Shimizu, T., Lila, A. S. A., Ishida, T., & Kiwada, H. (2015) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b14-00653 · Cited by 62 · see citing works
Self-citationInfusion reactions and their management
Mayer, L., & Young, Y. (2006) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2006.09.006 · Cited by 59 · see citing works
Li, C., Cao, J., Wang, Y., Zhao, X., Deng, C., Wei, N., Yang, J., & Cui, J. (2012) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.23254 · Cited by 57 · see citing works
Ma, Y., Yang, Q., Wang, L., Zhou, X., Zhao, Y., & Deng, Y. (2011) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2011.11.014 · Cited by 57 · see citing works
Mechanism of nanoparticle-induced hypersensitivity in pigs: complement or not complement?
Szebeni, J. (2018) · Drug Discovery Today · doi:10.1016/j.drudis.2018.01.025 · Cited by 56 · see citing works
Self-citationKloos, R. Q. H., van der Sluis, I. M., Mastrobattista, E., Hennink, W. E., Pieters, R., & Verhoef, J. (2019) · British Journal of Haematology · doi:10.1111/bjh.16254 · Cited by 56 · see citing works
Structural basis of polyethylene glycol recognition by antibody
Lee, C., Su, Y.-C., Ko, T., Lin, L., Yang, C.-Y., Chang, S. S.-C., Roffler, S. R., & Wang, A. H. ‐. (2020) · Journal of Biomedical Science · doi:10.1186/s12929-019-0589-7 · Cited by 56 · see citing works
Molecular insights for the biological interactions between polyethylene glycol and cells
Xu, L., Yang, J., Bai, X., Zhang, C., Shi, L., Wu, C., Su, Y., Jin, X., Liu, Y., & Zhu, X. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.09.002 · Cited by 53 · see citing works
Protein PEGylation for the design of biobetters: from reaction to purification processes
Santos, J. H. P. M., Torres‐Obreque, K. M., Meneguetti, G. P., et al. (2018) · Brazilian Journal of Pharmaceutical Sciences · doi:10.1590/s2175-97902018000001009 · Cited by 46 · see citing works
Human Clinical Relevance of the Porcine Model of Pseudoallergic Infusion Reactions
Szebeni, J., & Bawa, R. (2020) · Biomedicines · doi:10.3390/biomedicines8040082 · Cited by 45 · see citing works
Self-citationZhang, P., Sun, F., Hung, H., Jain, P. R., Leger, K. J., & Jiang, S. (2017) · Analytical Chemistry · doi:10.1021/acs.analchem.7b02447 · Cited by 36 · see citing works
Poppenborg, S. M., Wittmann, J., Walther, W., Brandenburg, G., Krähmer, R., Baumgart, J., & Leenders, F. (2016) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2016.06.007 · Cited by 35 · see citing works
Calabrese, L. H., Kavanaugh, A., Yeo, A. E. T., & Lipsky, P. E. (2017) · Arthritis Research & Therapy · doi:10.1186/s13075-017-1396-8 · Cited by 32 · see citing works
Vitreous Injections of Pegaptanib Sodium Triggering Allergic Reactions
Steffensmeier, A., Azar, A., Fuller, J. J., et al. (2006) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2006.10.007 · Cited by 30 · see citing works
Lila, A. S. A., Ichihara, M., Shimizu, T., Ishida, T., & Kiwada, H. (2013) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b13-00562 · Cited by 28 · see citing works
Self-citationFischbach, M., Wühl, E., Reigner, S. C. M., et al. (2017) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.03570417 · Cited by 22 · see citing works
Browne, E. K., Moore, C., Sykes, A. D., et al. (2017) · Journal of Pediatric Oncology Nursing · doi:10.1177/1043454217741868 · Cited by 22 · see citing works
Dong, H., Mora, J. R., Brockus, C. L., Chilewski, S. D., Dodge, R. W., Merrifield, C., Dickerson, W. M., & Desilva, B. S. (2015) · The AAPS Journal · doi:10.1208/s12248-015-9799-4 · Cited by 21 · see citing works
Lin, W.-W., Hsieh, Y.-C., Cheng, Y., et al. (2016) · Analytical Chemistry · doi:10.1021/acs.analchem.6b03614 · Cited by 21 · see citing works
PEGylation and anti-PEG antibodies
Lila, A. S. A., Shimizu, T., & Ishida, T. (2018) · Elsevier eBooks · doi:10.1016/b978-0-08-101750-0.00003-9 · Cited by 21 · see citing works
Self-citationA Cell Assay for Detecting Anti-PEG Immune Response against PEG-Modified Therapeutics
Shimizu, T., Lila, A. S. A., Awata, M., Kubo, Y., Mima, Y., Hashimoto, Y., Ando, H., Okuhira, K., Ishima, Y., & Ishida, T. (2018) · Pharmaceutical Research · doi:10.1007/s11095-018-2505-3 · Cited by 20 · see citing works
Self-citationAnti-PEG IgM Production via a PEGylated Nano-Carrier System for Nucleic Acid Delivery
Ichihara, M., Moriyoshi, N., Lila, A. S. A., Ishida, T., & Kiwada, H. (2012) · Methods in molecular biology · doi:10.1007/978-1-62703-140-0_4 · Cited by 19 · see citing works
Self-citationStaudacher, D. L., Putz, V., Heger, L. A., et al. (2017) · European Heart Journal Acute Cardiovascular Care · doi:10.1177/2048872617703065 · Cited by 18 · see citing works
Relative safety of peginesatide and epoetin alfa
Weinhandl, E. D., Gilbertson, D. T., Collins, A. J., et al. (2014) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.3655 · Cited by 14 · see citing works
Delayed hypersensitivity reaction related to the use of pegfilgrastim
Dadla, A., Tannenbaum, S. H., Yates, B., et al. (2014) · Journal of Oncology Pharmacy Practice · doi:10.1177/1078155214542493 · Cited by 13 · see citing works
Kenny, G. E., & Dunsmoor, C. L. (1987) · PubMed · Cited by 13 · see citing works
Larimore, K., Nguyen, T., Badillo, B., et al. (2019) · Journal of Immunological Methods · doi:10.1016/j.jim.2019.03.004 · Cited by 11 · see citing works
Lila, A. S. A., Szebeni, J., & Ishida, T. (2019) · doi:10.1201/b22372-25 · Cited by 7 · see citing works
Self-citationDesign and Development of Approved Nanopharmaceutical Products
Bawa, R., Audette, G. F., & Rubinstein, I. (2016) · doi:10.1201/b19915-18 · Cited by 6 · see citing works
Challenges and Risks of Nanotechnology in Medicine: An Immunologist's Point of View
Szebeni, J. (2016) · doi:10.1002/9783527692057.ch7 · Cited by 4 · see citing works
Self-citationNanotechnology for Human Health
Savage, N., Gorman, M. E., & Street, A. (2013) · doi:10.1201/b14865-6 · Cited by 3 · see citing works
Pegloticase: withdrawal of its European marketing authorisation is welcome.
(2017) · PubMed · Cited by 3 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Bawa, J. Szebeni, T.J. Webster, G.F. Audette (Eds.), Immune Effects of Biopharmaceuticals and Nanomedicines, Pan Stanford Publishing Pte. Ltd., Singapore 2018, pp. 771-800.
Cited by
Sorted by citations
mRNA vaccines for infectious diseases: principles, delivery and clinical translation
Chaudhary, N., Weissman, D., & Whitehead, K. A. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00283-5 · Cited by 1,555 · see citing works
Ndeupen, S., Qin, Z., Jacobsen, S., Bouteau, A., Estanbouli, H., & Igyártó, B. Z. (2021) · iScience · doi:10.1016/j.isci.2021.103479 · Cited by 678 · see citing works
A Comprehensive Review of mRNA Vaccines
Gote, V., Bolla, P. K., Kommineni, N., Butreddy, A., Nukala, P. K., Palakurthi, S. S., & Khan, W. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032700 · Cited by 457 · see citing works
Engineering nano-drug biointerface to overcome biological barriers toward precision drug delivery
Waheed, S., Li, Z., Zhang, F., Chiarini, A., Armato, U., & Wu, J. (2022) · Journal of Nanobiotechnology · doi:10.1186/s12951-022-01605-4 · Cited by 259 · see citing works
Padín-González, E., Lancaster, P., Bottini, M., Gasco, P., Tran, L., Fadeel, B., Wilkins, T., & Monopoli, M. P. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.882363 · Cited by 166 · see citing works
Non-immunotherapy application of LNP-mRNA: Maximizing efficacy and safety
Vlatkovic, I. (2021) · Biomedicines · doi:10.3390/biomedicines9050530 · Cited by 112 · see citing works
Foreign body response to synthetic polymer biomaterials and the role of adaptive immunity
Kyriakides, T. R., Kim, H.-J., Zheng, C., Harkins, L., Tao, W., & Deschenes, E. (2022) · Biomedical Materials · doi:10.1088/1748-605x/ac5574 · Cited by 106 · see citing works
Targeting oncogenic KRAS with molecular brush-conjugated antisense oligonucleotides
Wang, D., Wang, Q., Wang, Y., Chen, P., Lu, X., Jia, F., Sun, Y., Sun, T., Zhang, L., Che, F., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2113180119 · Cited by 43 · see citing works
Wang, K., Yang, R., Li, J., Wang, H., Wan, L., & He, J. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1591438 · Cited by 27 · see citing works
- Authors
- Kozma, G. T., Shimizu, T., Ishida, T., & Szebeni, J.
- Affiliations
- Semmelweis University (HU)
- Tokushima University (JP)
- Venue
- Advanced Drug Delivery Reviews
- Publisher
- Elsevier BV
- Published
- 2020
- Volume
- 154-155
- Pages
- 163-175
- ISSN
- 0169-409X (ISSN-L)
- OpenAlex
- W3046633757
- Cited by
- 696
- References
- 105
- Citations by year
- 2026: 139 · 2025: 143 · 2024: 100 · 2023: 127 · 2022: 106 · 2021: 72 · 2020: 8
- FWCI
- 5.23
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Advanced Drug Delivery Reviews (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (publishedVersion, cc-by-nc-nd)
- Funders
- European Union Horizon 2020 (825828)
- Applied Materials and Nano- technology Center of Excellence, Miskolc University
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
- Keywords
- anti-PEG antibodies, polyethylene glycol, PEGylation, accelerated blood clearance, hypersensitivity, complement activation, anti-drug antibodies, IgM and IgG antibodies, immunogenicity, drug safety, anaphylaxis
- MeSH terms
- Animals, Antibodies, Biological Assay, Humans, Polyethylene Glycols, Nanomedicine
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
