Abstract
Monocolonal antibodies are valuable potential new tools for meeting unmet needs in treating infectious dieseases and to provide alternatives and supplements to antibiotics in these times of growing resistance. Especially when considering the ability to screen for antibodies reacting to very diverse target antigens and the ability to design and engineer them to work specifically to hit and overcome their strategies, like toxins and their hiding in specific cells to evade the immuneresponse and their special features enabling killing of the infectious agents and or the cells harbouring them. Antibodies are generally very safe and adverse effects of treatments with therapeutic antibodies are usually related to exaggeration of the intended pharmacology. In this chapter general safety considerations for the use of antibodies is reviewed and the general procedures for nonclinical testing to support their clinical development. Special considerations for anti-infective mAb treatments are provided including the special features that makes nonclinical safety programs for anti-infective mAbs much more simple and restricted. However at a cost since only limited information for clinical safety and modeling can be derived from such programs. Then strategies for optimally designing antibodies are discussed including the use of combination of antibodies. Finally ways to facilitate development of more than the currently only three approved mAb based treatments are discussed with a special focus on high costs and high price and how collaboration and new strategies for development in emerging markets can be a driver for this.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Behring EA, Kitasato S (1890) Ueber das zustandekommen der diptherie-immunität und der tetanus-immunität bei thieren. Deutch Med Woch 49:1113–1114
Klemperer G, Klemperer F (1891) Versuche uber immunisirung und heilung bei der pneumokokkeninfection. Berlin Klin Wochenschr 28:833–835
Flexner S, Jobling JW (1908) Serum treatment of epidemic cerebro-spinal meningitis. J Exp Med 10:141–195
Köhler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495–497
Casadevall A, Dadachova E, Pirofski LA (2004) Passive antibody therapy for infectious diseases. Nat Rev Microbiol 2:695–703
Chatenoud L, Bluestone JA (2007) CD3-specific antibodies: a portal to the treatment of autoimmunity. Nat Rev Immunol 7(8):S. 622–S. 632. PMID 17641665
Baldo BA (2016) Safety of biologics therapies. Monoclonal antibodies, cytokines, fusion proteins, hormones, enzymes, coagulation proteins, vaccines, botulinum toxins. © Springer International Publishing Switzerland 2016, ISBN:978-3-319-30470-0; 29–214
Cai HH (2016) Therapeutic monoclonal antibodies approved by FDA in 2015. MOJ Immunol 3(2):00087
Cai HH (2017) Therapeutic monoclonal antibodies approved by FDA in 2016. MOJ Immunol 5(1):00145
Smith GP (1985). Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Science; 228:1315–7; PMID: 4001944. https://doi.org/10.1126/science.4001944
Chan CEZ, Angeline LPC, MacAry PA, Hanson BJ (2014) The role of phage display in therapeutic antibody discovery. Int Immunol. https://doi.org/10.1093/intimm/dxu082
Ouisse L-H, Gautreau-Rolland L, Devilder M-C, et al (2017) Antigen-specific single B cell sorting and expression-cloning from immunoglobulin humanized rats: a rapid and versatile method for the generation of high affinity and discriminative human monoclonal antibodies. BMC https://doi.org/10.1186/s12896-016-0322-5Biotechnol 17:3. https://doi.org/10.1186/s12896-016-0322-5
Murphy AJ, Macdonald LE, Stevens S, Karow M, Dore AT, Pobursky K, Huang TT, Poueymirou WT, Esau L, Meola M, Mikulka W, Krueger P, Fairhurst J, Valenzuela DM, Papadopoulos N, Yancopoulos GD (2014) Mice with megabase humanization of their immunoglobulin genes generate antibodies as efficiently as normal mice. Proc Natl Acad Sci U S A 111(14):5153–5158. https://doi.org/10.1186/s12896-016-0322-5. Epub 2014 Mar 25. PubMed PMID: 24706856; PubMed Central PMCID: PMC3986188
Leila Rahbarnia L, Farajnia S, Hossein Babaei H, Majidi J, Veisi K, Ahmadzadeh V, Akbari B (2017) Evolution of phage display technology: from discovery to application. J Drug Target 25(3):216–224. https://doi.org/10.1080/1061186X.2016.1258570
Breker OH, Sandlie I (2003) Therapeutic antibodies for human diseases at the dawn of the twenty-first century. Nat Rev Drug Discov 2:52–62
Hansel TT, Kropshofer H, Singer T, Mitchell JA, George AJT (2010) The safety and side effects of monoclonal antibodies. Nat Rev Drug Discov 9:325–338
Stebbings R, Findlay L, Edwards C, Eastwood D, Bird C, North D, Mistry Y, Paula D, Liefooghe E, Cludts I, Fox B, Tarrant G, Robinson J, Meager T, Dolman C, Thorpe SJ, Bristow A, Wadwa M, Thorpe R, Poole S (2007) “Cytokine Storm” in the Phase I Trial of monoclonal antibody TGN1412: better understanding the causes to improve preclinical testing of immunotherapeutics. J Immunol 179:3325–3331
Eastwood D, Bird C, Dilger P, Hockley J, FindlayL TSJ, Wadwa M, Thorpe R, Stebbings R (2013) Severity of the TGN1412 trial disaster cytokine storm correlated with IL-2release. Br J Clin Pharmacol 76(2):299–315
WHO/ PHARM S/NOM 1570 (1997) Guidelines On the use of international Nonproprietary Names (INNs) For Pharmaceutical Substances
World Heath Organisation Recommended INN: List 77 (2017) International Nonproprietary Names for Pharmaceutical Substances. WHO Drug Inform 31(1)
Eastwood D, Findlay L, Pool S, Bird C, Wadwa M, Moore M, Burns C, Thorpe R, Stebbings R (2010) Monoclonal antibody TGN1412 trial failure explained by species differences in CD28 expression on CD4+ effector memory T-cells. Br J Pharmacol 161(3):512–526
Stebbings R, Eastwood D, Pool S, Thorpe R (2013) After TGN1412: recent developments in cytokine release assays. J Immunotoxicol 10(1):75–82
Finco D, Grimalsi C, Fort M, Walker M, Kiessling A, Wolf B, Salcedo T, Faggioni R, Schneider A, Ibraghimov A, Scesney S, Serna D, Prell R, Stebbings R, Narayanan PK (2014) Cytokine release assays: current practices and future directions. Cytokine 66(2):143–155
Duff GD Expert Scientific Group on phase one clinical trials. Final report 30th November 2006. TSO@Blackwell. Online www.tsoshop.co.uk. ISBN-10 0 11 703722 2
European Medicines Agency.1 September 2007. Guideline on strategies to identify and mitigate risks for first in human clinical trials with investigational medicinal products. EMEA/CHMP/SWP/28367/07
Flipse J, Diosa-Toro MA, Hoornweg TE, van de Pol DPI, Urcuqui-Inchima S, Smit JM (2016) Antobody-dependent enhancement of dengue virus infection in primary human macrophages; balancing higher fusion against antiviral responses. Sci Rep 6:29201
Chan KR, Ong EZ, Mok DZL, Ooi EE (2015) Fc receptors and their influence on efficacy of therapeutic antibodies for treatment of viral diseases. Expert Rev Anti Infect Ther 13(11):1351–1360
Mirabet M, Barrabes JA, Quiroga A, Garcia-Dorado D (2008) Platelet pro-aggregatory effects of CD40L monoclonal antibody. Mol Immunol 45(4):937–944
Lacouture M (2006) Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat Rev Cancer 6:803–812
Wolach O, Bairey O, Lahav M (2010) Late-onset neutropenia after rituximab treatment – case series and comprehensive review of the literature. Medicine 89(5):308–318
Leach MW, Halpern WG, Johnson CW, Roiko JL, MacLachlan TK, Chan CM, Galbreath EJ, Ndifor AM, Blasset DL, Polack E, Cavagnaro JA (2010) Use of tissue cross-reactivity studies in the development of antibody-based biopharmaceuticals: history, experience, methodology, and future directions. Toxicol Pathol 38(7):1138–1166
Brennan FR, Dill Morton L, Spindeldreher S, Kiessling A, Allenspach R, Hey A, Muller PY, Frings W, Sims J (2010) Safety and immunotoxicity assessment of immunomodulatory monoclonal antibodies. mAbs 2(3):233–255
DeSesso JM, Williams AL, Ahuja A, Bowman CJ, Hurtt ME (2012) The Placenta, transfer of immunoglobulins, and safety assessment of biopharmaceuticals in pregnancy. Crit Rev Toxicol 42(3):185–210
Pentsuk N, van der Laan JW (2009) An interspecies comparison of placental antibody transfer: new insights into developmental toxicity testing of monoclonal antibodies. Birth Defects Res B Dev Reprod Toxicol 86(4):328–244
Lansita AL, Mounho-Zamora B (2015) The development of therapeutic monoclonal antibodies: overview of the nonclinical safety assessment. Curr Pain Headache Rep 19(2):1–9
Jarvis P, Srivastav S, Vogelwedde E, Stewart J, Mitchard T, Weinbauer GF (2010) The cynomolgus monkey as a model for developmental toxicity studies: variability of pregnancy losses, statistical power estimates and group size considerations. Birth Defects Research Part B 89:175–187
Aitken AE, Richardson TA, Morgan ET (2006) Regulation of drug-metabolizing enzymes and transporters in inflammation. Annu Rev Pharmacol toxicol 46:123–149
Morgan ET (2009) Impact of infectious and inflammatory disease on cytochrome P450-mediated drug metabolism and pharmacokinetics. Clin Pharmacol Ther 85(4):434–438
Lazar GA, Dang W, Karki S, Vafa O, Peng JS, Hyun L, Chan C, Chung HS, Eivazi A, Yoder SC (2006) Engineered antibody Fc variants with enhanced effector function. Proc Natl Acad Sci USA 103:4005–4010
Shields RL, Namenuk AK, Hong K, Meng YG, Rae J, Briggs J, Xie D, Lai J, Stadlen A, Li B (2001) High resolution mapping of the binding site on human IgG1 for FcγRI, FcγRII, FcγRIII, and FcRn and design of IgG1 variants with improved binding to the FcγR. J Biol Chem 276:6591–6604
Stewart R, Thom G, Levens M, Güler-Gane G, Holgate R, Rudd PM, Webster C, Jermutus L, Lund J (2011) A variant human IgG1-Fc mediates improved ADCC. Protein Eng Des Sel 24:671–678
Niwa R, Hatanaka S, Shoji-Hosaka E, Sakurada M, Kobayashi Y, Uehara A, Yokoi H, Nakamura K, Shitara K (2004) Enhancement of the antibody-dependent cellular cytotoxicity of low-fucose IgG1 is independent of Fc-gammaRIIIa functional polymorphism. Clin Cancer Res 10:6248–6255
Hezareh M, Hessell AJ, Jensen RC, van de Winkel JGJ, Parren PWHI (2001) Effector function activities of a panel of mutants of a broadly neutralizing antibody against human immunodeficiency virus type 1. J Virol 75:12161–12168
Hessell AJ, Hangartner L, Hunter M, Havenith CD, Beursken FJ, Bakker JM, Lanigan CM, Landucci G, Forthal DN, Parren PW, Marx PA, Burton DR (2007) Fc receptor but not complement binding is important in antibody protection against HIV. Nature 449(7158):101–104
Dall’Acqua WF, Kiener PA, Wu H (2006) Properties of human IgG1s engineered for enhanced binding to the neonatal Fc receptor (FcRn). J Biol Chem 281:23514–23524
Bregenholt S, Jensen A, Lantto J, Hyldig S, Haurum J (2006) Recombinant human polyclonal antibodies: a new class of therapeutic antibodies against viral infections. Curr Pharm Des 12:2007–2015
Flego M, Ascione A, Cianfriglia M, Vella S (2013) Clinical development of monoclonal antibody-based therapy drugs in HIV and HCV diseases. BMC Med 11:1–17
de Kruif J, Bakker ABH, Marissen WE, Arjen Kramer R, Throsby M, Rupprecht CE, Goudsmit J (2007) A human monoclonal antibody cocktail as a novel component of rabies post-exposure prophylaxis. Annu Rev Med 50:359–368
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer International Publishing AG, part of Springer Nature
About this chapter
Cite this chapter
Hey, A.S. (2017). Safety and General Considerations for the Use of Antibodies in Infectious Diseases. In: Lim, T. (eds) Recombinant Antibodies for Infectious Diseases. Advances in Experimental Medicine and Biology, vol 1053. Springer, Cham. https://doi.org/10.1007/978-3-319-72077-7_13
Download citation
DOI: https://doi.org/10.1007/978-3-319-72077-7_13
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-72076-0
Online ISBN: 978-3-319-72077-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)