Optimized nonclinical safety assessment strategies supporting clinical development of therapeutic monoclonal antibodies targeting inflammatory diseases

Drug Development Research

Volumn 75, Issue 3, 2014, Pages 115-161

  Brennan, Frank R ^a   Cauvin, Annick ^a   Tibbitts, Jay ^a   Wolfreys, Alison ^a  

^a UCB PHARMA   (Belgium)

Author keywords

autoimmunity; cancer; immunosuppression; infection; inflammation; monoclonal antibody; nonclinical safety; reproductive toxicity

Indexed keywords

ABATACEPT; ADALIMUMAB; ALEFACEPT; ALEMTUZUMAB; BASILIXIMAB; BELATACEPT; BELIMUMAB; BENRALIZUMAB; BRODALUMAB; CANAKINUMAB; CERTOLIZUMAB PEGOL; DACLIZUMAB; ECULIZUMAB; EFALIZUMAB; ETANERCEPT; GEVOKIZUMAB; GOLIMUMAB; INFLIXIMAB; IXEKIZUMAB; LEBRIKIZUMAB; MEPOLIZUMAB; MONOCLONAL ANTIBODY; NATALIZUMAB; OKT 3; OMALIZUMAB; RESLIZUMAB; RITUXIMAB; SARILUMAB; SECUKINUMAB; SIRUKUMAB; TOCILIZUMAB; UNINDEXED DRUG; USTEKINUMAB; ANTIINFLAMMATORY AGENT; IMMUNOLOGIC FACTOR;

ANAPHYLAXIS; ANTIBODY SPECIFICITY; AUTOIMMUNE DISEASE; AUTOIMMUNITY; CANCER RISK; CROSS REACTION; CYTOKINE RELEASE SYNDROME; DRUG HALF LIFE; DRUG INDICATION; DRUG SAFETY; FERTILITY; GRAFT REJECTION; HOST RESISTANCE; HUMAN; IMMUNOPHARMACOLOGY; IMMUNOREACTIVITY; IMMUNOSUPPRESSIVE TREATMENT; IMMUNOTOXICITY; IN VITRO STUDY; INFECTION RISK; INFLAMMATION; INFLAMMATORY DISEASE; INFUSION; NONHUMAN; PREGNANCY; REVIEW; RISK ASSESSMENT; ANIMAL; DRUG SCREENING; PROCEDURES;

ANIMALS; ANTI-INFLAMMATORY AGENTS; ANTIBODIES, MONOCLONAL; DRUG EVALUATION, PRECLINICAL; HUMANS; IMMUNOLOGIC FACTORS; INFLAMMATION;

EID: 84900486102     PISSN: 02724391     EISSN: 10982299     Source Type: Journal    
DOI: 10.1002/ddr.21173     Document Type: Review

References (229)

1. Agoram BM,. 2009. Use of pharmacokinetic/pharmacodynamic modeling for starting dose selection in first-in-human trials of high-risk biologics. Br J Clin Pharmacol 67: 153-160.
2. Ahmad ZA, Yeap SK, Ali AM, Ho WY, Alitheen NB, Hamid M,. 2012. scFv antibody: principles and clinical application. Clin Dev Immunol 2012: 980250. doi: 10.1155/2012/980250; Epub 2012 Mar 15; (15 pages).
3. Amevive. 2002. BLA review, Pharmacology and Toxicology Assessment, FDA. available at http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/ HowDrugsareDevelopedandApproved/ApprovalApplications/ %20TherapeuticBiologic%20Applications/ucm086014.pdf Accessed 8th April, 2014.
4. Atzeni F, Talotta R, Salaffi F, Cassinotti A, Varisco V, Battellino M, Ardizzone S, Pace F, Sarzi-Puttini P,. 2013. Immunogenicity and autoimmunity during anti-TNF therapy. Autoimmun Rev 12: 703-708.
5. Auyeung-Kim DJ, Devalaraja MN, Migone T-S, Cai W, Chellman GJ,. 2009. Developmental and peri-postnatal study in cynomolgus monkeys with belimumab, a monolconal antibody directed against B-lymphocyte stimulator. Reprod Toxicol 28: 443-455.
6. Baldrick P,. 2010. Juvenile animal testing in drug development-is it useful? Regul Toxicol Pharmacol 57: 291-299.
7. Baldrick P,. 2011. Safety evaluation of biological drugs: what are toxicology studies in primates telling us? Regul Toxicol Pharmacol 59: 227-236.
8. Balkwill F,. 2009. Tumor necrosis factor and cancer. Nat Rev 9: 361-371.
9. Barr BB, Benton EC, McLaren K, Bunney MH, Smith IW, Blessing K, Hunter JA,. 1989. Human papilloma virus infection and skin cancer in renal allograft recipients. Lancet 1: 124-129.
10. Beck A, Reichert JM,. 2013. Approval of the first biosimilar antibodies in Europe: a major landmark for the biopharmaceutical industry. MAbs 5: 621-623.
11. Becker C, Fantini MC, Wirtz S, Nikolaev A, Lehr HA, Galle PR, Rose-John S, Neurath MF,. 2005. IL-6 signaling promotes tumor growth in colorectal cancer. Cell Cycle 4: 217-220.
12. Bellocq A, Antoine M, Flahault A, Philippe C, Crestani B, Bernaudin JF, Mayaud C, Milleron B, Baud L, Cadranel J,. 1998. Neutrophil alveolitis in bronchioloalveolar carcinoma: induction by tumor-derived interleukin-8 and relation to clinical outcome. Am J Pathol 152: 83-92.
13. Bendele A., Seely J., Richey C., Sennello G., Shopp G,. 1998. Short communication: renal tubular vacuolation in animals treated with polyethylene-glycol-conjugated proteins. Toxicol. Sci. 42: 152-157.
14. Benlysta. 2010. European public assessment report. Available here: http://www.ema.europa.eu%20/docs/%20en-GB/document-library/EPAR-Product- Information/human/002015/WC500110150.pdf Accessed 8th April, 2014.
15. Bielekova B, Becker BL,. 2010. Monoclonal antibodies in MS. Neurology 74 (Suppl. 1): S31-S40.
16. Binz HK, Amstutz P, Plückthun A,. 2005. Engineering novel binding proteins from non immunoglobulin domains. Nat Biotechnol 23: 1257-1268.
17. Bisikirska B, Colgan J, Luban J, Bluestone JA, Herold KC,. 2005. TCR stimulation with modified anti-CD3 mAb expands CD8 + T cell population and induces CD8 + CD25 + Tregs. J Clin Invest 115: 2904-2913.
18. Bowden GT, Jaffe D, Andrews K,. 1990. Biological and molecular aspects of radiation carcinogenesis in mouse skin. Radiat Res 121: 235-241.
19. Bowman CJ, Chmielewski G, Oneda S, Finco D, Boucher MA, Todd M,. 2010. Embryo-fetal developmental toxicity of figitumumab, an anti-insulin-like growth factor-1 receptor (IGF-1R) monoclonal antibody, in cynomolgus monkeys. Birth Defects Res B Dev Reprod Toxicol 89: 326-338.
20. Bowman CJ, Breslin WJ, Connor AV, Martin PL, Moffat GJ, Sivaraman L, Tornesi MB, Chivers S,. 2013. Placental transfer of Fc-containing biopharmaceuticals across species, an industry survey analysis. Birth Defects Res B Dev Reprod Toxicol 98: 459-485. doi: 10.1002/bdrb.21089; Epub 2014 Jan 3.
21. Brennan FR, Morton LD, Spindeldreher S, Kiessling A, Allenspach R, Hey A, Mueller P, Frings W, Sims J,. 2010. Safety and immunotoxicity assessment of immunomodulatory monoclonal antibodies. MAbs 2: 233-255.
22. Bruhns P, Iannascoli B, England P, Mancardi DA, Fernanedez N, Jorieux S, Daëron M,. 2009. Specificity and affinity of human Fcgamma receptors and their polymorphic variants for human IgG subclasses. Blood 113: 3716-3725.
23. Brunda MJ, Luistro L, Warrier RR, Wright RB, Hubbard BR, Murphy M, Wolf SF, Gately MK,. 1993. Antitumor and antimetastatic activity of interleukin 12 against murine tumors. J Exp Med 78: 1223-1230.
24. Bugelski PJ, Martin PL,. 2012. Concordance of preclinical and clinical pharmacology and toxicology of therapeutic monoclonal antibodies and fusion proteins: cell surface targets. Br J Pharmacol 166: 823-846.
25. Bugelski PJ, Herzyk DJ, Rehm S, Harmsen AG, Gore EV, Williams DM, Maleeff BE, Badger AM, Truneh A, O'Brien SR, et al. 2000. Preclinical development of keliximab, a primatized anti-CD4 monoclonal antibody, in human CD4 transgenic mice: characterization of the model and safety studies. Hum Exp Toxicol 19: 230-243.
26. Bugelski PJ, Sachs C, Cornacoff J, Martin P, Treacy G,. 2008. Immunomodulatory biopharmaceuticals and risk of neoplasia. In:, Cavagnaro JA, editor. Preclinical safety evaluation of biopharmaceuticals. Hoboken, NJ: John Wiley & Son. p 601-632.
27. Bugelski PJ, Volk A, Walker MR, Krayer JH, Martin P, Descotes J,. 2010. Critical review of preclinical approaches to evaluate the potential of immunosuppressive drugs to influence human neoplasia. Int J Toxicol 29: 435-466.
28. Burleson GR, Burleson FG,. 2007. Influenza virus host resistance model. Methods 41: 31-37.
29. Burleson GR, Burleson FG,. 2008. Testing human biologicals in animal host resistance models. J Immunotoxicol 5: 23-31.
30. Burns-Naas LA, Hastings KL, Ladics GS, Makris SL, Parker GA, Holsapple MP,. 2008. What's so special about the developing immune system? Int J Toxicol 27: 223-254.
31. Bussiere JL, Martin P, Morner M, Couch J, Flaherty M, Andrews L, Beyer J, Horvath C,. 2009. Alternative strategies for toxicity testing of species-specific biopharmaceuticals. Int J Toxicol 28: 230-253.
32. Büttel IC, Chamberlain P, Chowers Y, Ehmann F, Greinacher A, Jefferis R, Kramer D, Kropshofer H, Lloyd P, Lubiniecki A, et al. 2011. Taking immunogenicity assessment of therapeutic proteins to the next level. Biologicals 39: 100-109.
33. Campath. 2001. FDA. Pharmacology review. Available at http://www.accessdata.fda.gov/drugsatfda-docs/nda/2000/103948-0000-Campath- PharmTox.pdf Accessed 8th April, 2008.
34. Campbell KJ, Detmer AM, Karl JA, Wiseman RW, Blasky AJ, Hughes AL, Bimber BN, O'Connor SL, O'Connor DH,. 2009. Characterization of 47 MHC class I sequences in Filipino cynomolgus macaques. Immunogenetics 61: 177-187.
35. Carbonatto M, Yu P, Bertolino M, Vigna E, Steidler S, Fava L, Daghero C, Roattino B, Onidi M, Ardizzone M, Peano S, Visich J, Janszen D, Dillon S, Ponce R,. 2008. Nonclinical safety, pharmacokinetics, and pharmacodynamics of atacicept. Toxicol Sci. 105: 200-210.
36. Carlock LL, Cowan LA, Oneda S, Hoberman A, Wang DD, Hanna R, Bussiere JL,. 2009. A comparison of effects on reproduction and neonatal development in cynomolgus monkeys given human soluble IL-4R and mice given murine soluble IL-4R. Regul Toxicol Pharmacol 53: 226-234.
37. Cavagnaro JA,. 2008. Preclinical evaluation of cancer hazard and risk of biopharmaceuticals. In:, Cavagnaro JA, editor. Preclinical safety evaluation of biopharmaceuticals. Hoboken, NJ: John Wiley & Son. p 209-240.
38. Chai C, White WL, Shea CR, Prieto VG,. 1999. Epstein Barr virus-associated lymphoproliferative-disorders primarily involving the skin. J Cutan Pathol 26: 242-247.
39. Chakravarty EF, Murray ER, Kelman A, Farmer P,. 2011. Pregnancy outcomes after maternal exposure to rituximab. Blood 117: 1499-1506.
40. Chan AC, Carter PJ,. 2010. Therapeutic antibodies for autoimmunity and inflammation. Nat Rev 10: 301-316.
41. Chapman K, Pullen N, Coney L, Dempster M, Andrew L, Bajramovic J, Baldrick P, Buckley B, Jacobs A, Hale G, et al. 2009. Preclinical development of monoclonal antibodies. Considerations for the use of non-human primates. MAbs 1: 505-516.
42. Chapman KL, Andrews L, Bajramovic JJ, Baldrick P, Black LE, Bowman CJ, Buckley LA, Coney LA, Couch J, Maggie Dempster A, et al. 2012. The design of chronic toxicology studies of monoclonal antibodies: implications for the reduction in use of non-human primates. Regul Toxicol Pharmacol 62: 347-354.
43. Chung CH, Mirakhur B, Chan E, Le QT, Berlin J, Morse M, Murphy BA, Satinover SM, Hosen J, Mauro D, et al. 2008. Cetuximab-induced anaphylaxis and IgE specific for galactose α-1,3-galactose. N Engl J Med 358: 1109-1117.
44. Cirée A, Michel L, Camilleri-Bröet S, Jean Louis F, Oster M, Flageul B, Senet P, Fossiez F, Fridman WH, Bachelez H, et al. 2004. Expression and activity of IL-17 in cutaneous T-cell lymphomas (mycosis fungoides and Sezary syndrome). Int J Cancer 112: 113-120.
45. Clarke J, Leach W, Pippig S, Joshi A, Wu B, House R, Beyer J,. 2004. Evaluation of a surrogate antibody for preclinical safety testing of an anti-CD11a monoclonal antibody. Regul Toxicol Pharmacol 40: 219-226.
46. Clarke J, Hurst C, Martin P, Vahle J, Ponce R, Mounho B, Heidel S, Andrews L, Reynolds T, Cavagnaro J,. 2008. Duration of chronic toxicity studies for biotechnology-derived pharmaceuticals: is 6 months still appropriate? Regul Toxicol Pharmacol 50: 2-22.
47. Clarke JB,. 2010. Mechanism of adverse drug reactions to biologics. Handb Exp Pharmacol 196: 453-474.
48. Cohen SM, Robinson D, MacDonald J,. 2001. Alternative models for carcinogenicity testing. Toxicol Sci 64: 14-19.
49. Coles AJ, Wing M, Smith S, Coraddu F, Greer S, Taylor C, Weetman A, Hale G, Chatterjee VK, Waldmann H, et al. 1999. Pulsed monoclonal antibody treatment and autoimmune thyroid disease in multiple sclerosis. Lancet 354: 1691-1695.
50. Crocker PR,. 2005. Siglecs in innate immunity. Curr Opin Pharmacol 5: 431-437.
51. da Silva A, Kronthaler U, Koppenburg V, Fink M, Meyer I, Papandrikopoulou A, Hofmann M, Stangler T, Visser J,. 2014. Target-directed development and preclinical characterization of the proposed biosimilar rituximab GP2013. Leuk Lymphoma. 2014 Jan 24. [published ahead of print].
52. de Jong-Tieben LM, Berkhout RJ, ter Schegget J, Vermeer BJ, de Fijter JW, Bruijn JA, Westendorp RG, Bouwes Bavinck JN,. 2000. The prevalence of human papilloma virus DNA in benign keratotic skin lesions of renal transplant recipients with and without a history of skin cancer is equally high: a clinical study to assess risk factors of keratotic skin lesions and skin cancer. Transplantation 69: 44-49.
53. Descotes J, Gouraud A,. 2008. Clinical immunotoxicity of therapeutic proteins. Expert Opin Drug Metab Toxicol 4: 1537-1549.
54. Dietert RR,. 2008. Developmental Immunotoxicology (DIT): windows of vulnerability, immune dysfunction and safety assessment. J Immunotoxicol 5: 401-412.
55. Dummer JS, Bound LM, Singh G, Atchison RW, Kapadia SB, Ho M,. 1984. Epstein-Barr virus-induced lymphoma in a cardiac transplant recipient. Am J Med 77: 179-184.
56. Eastwood D, Findlay L, Poole S, Bird C, Wadhwa 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: 512-526.
57. Egberts JH, Cloosters V, Noack A, Schniewind B, Thon L, Klose S, Kettler B, von Forstner C, Kneitz C, Tepel J, et al. 2008. Anti-tumor necrosis factor therapy inhibits pancreatic tumor growth and metastasis. Cancer Res 68: 1443-1450.
58. EMA. 2012. Guideline on similar biological medicinal products containing monoclonal antibodies: non-clinical and clinical issue Available at: http://www.ema.europa.eu/docs/en-GB/document-%20library/Scientific-guideline/ 2012/06/WC500128686.pdf Accessed 8th April, 2014.
59. EMEA. 2005. Guideline on similar biological medicinal products. Available at: http://www.ema.%20europa.eu/docs/en-GB/document-library/Scientific- guideline/2009/09/WC500003517.pdf Accessed 8th April, 2014.
60. EMEA. 2007. Guideline on strategies to identify and mitigate risks for First-in-human clinical trials with investigational medicinal products. Available at: http://www.ema.europa.eu/docs/en-%20GB/%20document-%20library/ %20Scientific-%20guideline/2009/09/WC500002988.pdf Accessed 8th April, 2014.
61. EMEA. 2008a. Guideline on the non-clinical development of fixed combinations of medicinal products. Available at: http://www.ema.europa.eu/docs/ en-GB/document-library/Scientific%20-guideline%20/2009/10/WC500003976.pdf Accessed 8th April, 2014.
62. EMEA. 2008b. Guideline on the need for non-clinical testing in juvenile animals of pharmaceuticals for paediatric indications. Available at: http://www.ema.europa.eu/docs/en-GB/document-library/%20Scientific-%20guideline/ 2009/09/WC500003305.pdf Accessed 8th April, 2014.
63. Farge D, Lebbé C, Marjanovic Z, Tuppin P, Mouquet C, Peraldi MN, Lang P, Hiesse C, Antoine C, Legendre C, et al. 1999. Human HV-8 and other risk factors for Kaposi's sarcoma in kidney transplant recipients. Transplantation 67: 1236-1242.
64. FDA. 1996. Guidance: demonstration of comparability of human biological products, including therapeutic biotechnology-derived products. Available at: http://www.fda.gov/Drugs/Guidance%20ComplianceRegulatoryInformation/Guidances/ ucm122879.htm Accessed 8th April, 2014.
65. FDA. 1997. Points to consider in the manufacture and testing of monoclonal antibody products for human use. Available at: http://www.fda.gov/ downloads/BiologicsBloodVaccines/Guidance%20ComplianceRegulatoryInformation/ OtherRecommendationsforManufacturers/UCM153182.pdf Accessed 8th April, 2014.
66. FDA. 2006. Guidance for industry: nonclinical safety evaluation of drug or biologic combinations. Available at: http://www.fda.gov/downloads/Drugs/ GuidanceComplianceRegulatoryInformation/%20Guidances/ucm079243.pdf Accessed 8th April, 2014.
67. FDA. 2012. Guidance for industry: scientific considerations in demonstrating biosimilarity to a reference product. Available at: http://www.fda.gov/downloads/Drugs/ GuidanceCompliance%20RegulatoryInformation%20/Guidances/UCM291128.pdf Accessed 8th April, 2014.
68. FDA. 2013. Guidance for industry: codevelopment of two or more new investigational drugs for use in combination. Available at: http://www.fda.gov/ downloads/Drugs/GuidanceComplianceRegulatory%20Information/Guidances/UCM236669. pdf Accessed 8th April, 2014.
69. Feng W, Cohen JI, Fischer S, Li L, Sneller M, Goldbach-Mansky R, Raab-Traub N, Delecluse HJ, Kenney SC,. 2004. Reactivation of latent EBV by Methotrexate: a potential contributor to methotrexate associated lympmoma. J Natl Cancer Inst 96: 1691-1702.
70. Finco D, Grimaldi C, Fort M, Walker M, Kiessling A, Wolf B, Salcedo T, Faggioni R, Schneider A, Ibraghimov A, et al. 2014. Cytokine release assays: Current practices and future directions. Cytokine 66: 143-155.
71. Flaherty MM, MacLachlan TK, Troutt M, Magee T, Tuaillon N, Johnson S, Stein KE, Bonvini E, Garman R, Andrews L,. 2012. Nonclinical evaluation of GMA161- an antihuman CD16 (FcγRIII) monoclonal antibody for treatment of autoimmune disorders in CD16 transgenic mice. Toxicol Sci 125: 299-309.
72. Fraser G, Smith CA, Imrie K, Meyer R, the Hematology Disease Site Group of Cancer Care Ontario's Program in Evidence-Based Care. 2007. Alemtuzumab in chronic lymphocytic leukemia. Curr Oncol 14: 96-109.
73. Fredericks C, Kvam K, Bear J, Crabtree G, Josephson S,. 2014. A case of progressive multifocal leukoencephalopathy in a lupus patient treated with belimumab. Lupus Feb 14. [Epub ahead of print].
74. Frigault MJ, June CH,. 2011. Predicting cytokine storms: it's about density. Blood 118: 6724-6726.
75. Garay RP, El-Gewely R, Armstrong JK, Garratty G, Richette P,. 2012. Antibodies against polyethylene glycol in healthy subjects and in patients treated with PEG-conjugated agents. Expert Opin Drug Deliv. 9: 1319-1323.
76. Genovese MC, Cohen S, Moreland L, Lium D, Robbins S, Newmark R, Bekker P, 20000223 Study Group. 2004. Combination therapy with etanercept and anakinra in the treatment of patients with rheumatoid arthritis who have been treated unsuccessfully with methotrexate. Arthritis Rheum 50: 1412-1419.
77. Geoly FJ,. 2013. Regulatory forum opinion piece: tissue cross-reactivity studies: what constitutes an adequate positive control and how do we report positive staining? Toxicol Pathol. 2013 Jul 11. [Epub ahead of print] No abstract available.
78. Germolec DR, Kashon M, Nyska A, Kuper CF, Portier C, Kommineni C, Johnson KA, Luster MI,. 2004. The accuracy of extended histopathology to detect immunotoxic chemicals. Toxicol Sci 82: 504-514.
79. Giragossian C, Clark T, Piché-Nicholas N, Bowman CJ,. 2013. Neonatal Fc receptor and its role in the absorption, distribution, metabolism and excretion of immunoglobulin G-based biotherapeutics. Curr Drug Metab 14: 764-790.
80. Gogishvili T, Langenhorst D, Lühder F, Elias F, Elflein K, Dennehy KM, Gold R, Hünig T,. 2009. Rapid regulatory T-cell response prevents cytokine storm in CD28 superagonist treated mice. PLoS ONE 4: e4643.
81. Goineau S, Lemaire M, Froget G,. 2013. Overview of safety pharmacology. Curr Protocol Pharmacol. 2013 Dec 2;63:Unit 10.1. doi: 10.1002/0471141755. ph1001s63.
82. Gommerman JL, Mackay F, Donskoy E, Meier W, Martin P, Browning JL,. 2002. Manipulation of lymphoid microenvironments in nonhuman primates by an inhibitor of the lymphotoxin pathway. J Clin Invest 110: 1359-1369.
83. Goodman JI,. 2001. A perspective on current and future uses of alternative for carcinogenicity testing. Toxicol Pathol 29: 173-176.
84. Grönwall C, Ståhl S,. 2009. Engineered affinity proteins-generation and applications. J Biotechnol 140: 254-269.
85. Haley P, Perry R, Ennulat D, Frame S, Johnson C, Lapointe JM, Nyska A, Snyder P, Walker D, Walter G, et al. 2005. STP position paper: best practice guideline for the routine pathology evaluation of the immune system. Toxicol Pathol 33: 404-407.
86. Haley PJ,. 2003. Species differences in the structure and the function of the immune system. Toxicology 188: 49-71.
87. Hall WC, Price-Schiavi SA, Wicks J, Rojko JL,. 2008. Tissue cross-reactivity studies for monolconal antibodies: predictive value and use for selection pf relevant aimal species for toxicity testing. In:, Cavagnaro JA, editor. Preclinical safety evaluation of biopharmaceuticals. Hoboken, NJ: John Wiley & Son. p 209-240.
88. Herceptin. 2010. FDA. Final labeling text. Available at: http://www.accessdata.fda.gov/drugsatfda%20-docs/label/2010/103792s5256lbl.pdf Accessed 8th April, 2014.
89. Herzyk D, Holsapple M,. 2007. Immunotoxicity evaluation by immune function tests: focus on the T-dependent antibody response. J Immunotoxicol 4: 143-147.
90. Herzyk DJ, Gore ER, Polsky R, Nadwodny KL, Maier CC, Liu S, Hart TK, Harmsen AG, Bugelski PJ,. 2001. Immunomodulatory effects of anti-CD4 antibody in host resistance against infections and tumors in human CD4 transgenic mice. Infect Immun 69: 1032-1043.
91. Honorati MC, Cattini L, Facchini A,. 2004. IL-17, IL-1beta and TNF-alpha stimulate VEGF production by dedifferentiated chondrocytes. Osteoarthritis Cartilage 12: 683-691.
92. Horton HM, Chu SY, Ortiz EC, Pong E, Cemerski S, Leung IW, Jacob N, Zalevsky J, Desjarlais JR, Stohl W, et al. 2011. Antibody-mediated coengagement of FcγRIIb and B cell receptor complex suppresses humoral immunity in systemic lupus erythematosus. J Immunol 186: 4223-4233.
93. Humira. 2002. FDA. Pharmacology and toxicology summary. Available at: http://www.fda.gov/%20downloads%20/Drugs/%20DevelopmentApproval%20Process/ %20HowDrugsareDevelopedandApproved/%20ApprovalApplications/ %20TherapeuticBiologicApplications/ucm092772.pdf Accessed 8th April, 2014.
94. Hunig T,. 2012. The storm has cleared: lessons from the CD28 superagonist TGN1412 trial. Nat Rev Immunol 12: 317-318.
95. Ibanez JP, Monteverde ML, Goldber J, Diaz MA, Turconi A,. 2005. Sirolimus in pediatric renal transplantation. Transplant Proc 37: 682-684.
96. ICH S7B. 2005. The non-clinical evaluation of the potential for delayed ventricular repolarisation (QT interval prolongation) by human pharmaceuticals. Available at: http://www.ich.org/LOB/media/%20MEDIA2192.%20pdf Accessed 8th April, 2014.
97. ICHM3 (R2). 2009. Nonclinical safety studies for the conduct of human clinical trials with pharmaceuticals. Available at: http://www.ema.europa.eu/ pdfs/human/ich/%20028695en.pdf Accessed 8th April, 2014.
98. ICHS1A. 1995. The need for long-term rodent carcinogenicity studies of pharmaceuticals. Available at: http://www.ema.europa.eu/docs/en-GB/document- library/Scientific-guideline/2009/09/%20WC500002699.pdf Accessed 8th April, 2014.
99. ICHS5(R2). 2005. Detection of toxicity to reproduction for medicinal products & toxicity to male fertility. Available at: http://www.ich.org/LOB/ media/MEDIA498.pdf Accessed 8th April, 2014.
100. ICHS6 (R1). 2009. Preclinical safety evaluation of biotechnology-derived pharmaceuticals. Step 2 Addendum. Available at: http://www.ich.org/LOB/media/ %20MEDIA5784.pdf Accessed 8th April, 2014.
101. ICHS7A. 2001. Safety pharmacology studies for human pharmaceuticals. Available at http://www.ich.org%20/LOB/media/MEDIA504.pdf Accessed 8th April, 2014.
102. ICHS8. 2004. Notes for guidance on immunotoxicity testing of human pharmaceuticals. Available at: http://www.ema.europa.eu%20/pdfs/human/ich%20/ 16723504en.pdf Accessed 8th April, 2014.
103. Ilaris. 2009. Toxicology summary. Available at: http://www.accessdata. fda.gov/drugsatfda-%20docs/nda/2009/125319 s000-%20PharmR-P2.pdf Accessed 8th April, 2014.
104. Ioachim HL,. 1990. The opportunistic tumors of immune deficiency. Adv Cancer Res 54: 301-317.
105. Irwin S,. 1968. Comprehensive observational assessment: a systematic, quantitative procedure for assessing the behavioral and physiological state of the mouse. Psychopharmacologia 13: 222-257.
106. Jarvis P, Srivastav S, Vogelwedde E, Stewart J, Mitchard T, Weinbauer GF,. 2010. The cynomolgus monkey as a model for developmetal toxicity studies: variability of pregancy losses. Statistical power estimates and group size considerations. Birth Defects Res B Dev Reprod Toxicol 89: 175-187.
107. Jawa V, Cousens LP, Awwad M, Wakshull E, Kropshofer H, De Groot AS,. 2013. T-cell dependent immunogenicity of protein therapeutics: preclinical assessment and mitigation. Clin Immunol 149: 534-555.
108. Jefferis R,. 2007. Antibody therapeutics: isotype and glycoform selection. Expert Opin Biol Ther 7: 1401-1413.
109. Jenkins C, Roberts J, Wilson R, Maclean MA, Shilito J, Walker JJ,. 2000. Evidence of a Th1-type response associated with recurrent miscarriage. Fertil Steril 73: 1206-1208.
110. Jin LP, Zhou YH, Zhu XY, Wank MY, Li DJ,. 2006. Adoptive tranfer of paternal antigen-hyporesponsive T cells facilitates a TH2 bias in peripheral lymphocytes and at materno-fetal interface in murine abortion-prone matings. Am J Reprod Immunol 56: 258-266.
111. Jones JL, Thompson SA, Loh P, Davies JL, Tuohy OC, Curry AJ, Azzopardi L, Hill-Cawthorne G, Fahey MT, Compston A, et al. 2013. Human autoimmunity after lymphocyte depletion is caused by homeostatic T-cell proliferation. Proc Natl Acad Sci USA 110: 20200-20205.
112. Jovanovic DV, Di Battista JA, Martel-Pelletier J, Reboul P, He Y, Jolicoeur FC, Pelletier JP,. 2001. Modulation of TIMP-1 synthesis by antiinflammatory cytokines and prostaglandin E2 in interleukin 17 stimulated human monocytes/macrophages. J Rheumatol 28: 712-718.
113. Kelley RF, Meng YG,. 2012. Methods to engineer and identify IgG1 variants with improved FcRn binding or effector function. Methods Mol Biol 901: 277-293.
114. Keystone EC,. 2011. Does anti-tumor necrosis factor-{alpha} therapy affect risk of serious infection and cancer in patients with rheumatoid arthritis?: a review of longterm data. J Rheumatol 38: 1552-1562.
115. Khader SA, Pearl JE, Sakamoto K, Gilmartin L, Bell GK, Jelley-Gibbs DM, Ghilardi N, deSauvage F, Cooper AM,. 2005. IL-23 compensates for the absence of IL-12p70 and is essential for the IL-17 response during tuberculosis but is dispensable for protection and antigen-specific IFN-gamma responses if IL-12p70 is available. J Immunol 175: 788-795.
116. Kimby E,. 2005. Tolerability and safety of rituximab (Mabthera). Cancer Treat Rev 31: 456-473.
117. Kita YF, Hosomichi K, Kohara S, Itoh Y, Ogasawara K, Tsuchiya H, Torii R, Inoko H, Blancher A, Kulski JK, et al. 2009. MHC class I A loci polymorphism and diversity in three Southeast Asian populations of cynomolgus macaque. Immunogenetics 61: 635-648.
118. Kleinschmidt-DeMasters BK, Tyler KL,. 2005. Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis. N Engl J Med 353: 369-374.
119. Kryczek I, Wei S, Zou L, Szeliga W, Vatan L, Zou W,. 2009. Endogenous IL-17 contributes to reduced tumor growth and metastasis. Blood 114: 357-359.
120. Lachmann HJ, Lowe P, Felix SD, Rordorf C, Leslie K, Madhoo S, Wittkowski H, Bek S, Hartmann N, Bosset S, et al. 2009. In vivo regulation of interleukin 1beta in patients with cryopyrin-associated periodic syndromes. J Exp Med 206: 1029-1036.
121. Langowski JL, Zhang X, Wu L, Mattson JD, Chen T, Smith K, Basham B, McClanahan T, Kastelein RA, Oft M,. 2006. IL-23 promotes tumor incidence and growth. Nature 442: 461-465.
122. Laskarin G, Kammerer U, Rukavina D, Thomson AW, Fernandez N, Blois SM,. 2007. Antigen-presenting cells and materno-fetal tolerance: an emerging role for dendritic cells. Am J Reprod Immunol 58: 255-267.
123. Leach M, Halpern WG, Johnson CW, Rojko JL, Maclachlan TK, Chan CM, Galbreath EJ, Ndifor AM, Blanset DL, Polack E, et al. 2010. Use of tissue cross-reactivity studies in the development of antibody-based biopharmaceuticals: history, experience, methodology and future directions. Toxicol Pathol 38: 1138-1166.
124. Lee PC, Wang YW, Su IJ, Lin YJ, Lei HY,. 1998. Immunosuppressive drugs and HHV-8 in a patient with renal transplant and Kaposi's sarcoma. Lancet 351: 1175-1176.
125. Leonardi CL, Toth D, Cather JC, Langley RG, Werther W, Compton P, Kwon P, Wetherill G, Curtin F, Menter A,. 2006. A review of malignancies observed during efalizumab (Raptiva) clinical trials for plaque psoriasis. Dermatology 213: 204-214.
126. Lewis RM,. 2008. Demonstration of comparability of a licensed product after a manufacturing change. In:, Cavagnaro JA, editor. Preclinical safety evaluation of biopharmaceuticals. Hoboken, NJ: John Wiley & Son. p 161-178.
127. Lindå H, von Heijne A, Major EO, Ryschkewitsch C, Berg J, Olsson T, Martin C,. 2009. Progressive multifocal leukoencephalopathy after natalizumab monotherapy. N Engl J Med 361: 1081-1087.
128. Lowe PJ, Tannenbaum S, Wu K, Lloyd P, Sims J,. 2010. On setting the first dose in man: quantitating biotherapeutic drug-target binding through pharmacokinetic and pharmacodynamic models. Basic Clin Pharmacol Toxicol 106: 195-209.
129. Luster MI, Portier C, Pait DG, Rosenthal GJ, Germolec DR, Corsini E, Blaylock BL, Pollock P, Kouchi Y, Craig W, et al. 1993. Risk assessment in immunotoxicology. II. Relationships between immune and host resistance tests. Fundam Appl Toxicol 21: 71-82.
130. Lynch C, Hart BW, Grewal IS,. 2009. Practical considerations for nonclinical safety evaluation of therapeutic monoclonal antibodies. MAbs 1: 2-11.
131. MacDonald J, French JE, Gerson RJ, Goodman J, Inoue T, Jacobs A, Kasper P, Keller D, Lavin A, Long G, et al. 2004. The utility of genetically modified mouse assays for identifying human carcinogens: a basic understanding and path forward. Toxicol Sci 77: 188-194.
132. Maeda A, Schneider SW, Kojima M, Beiddert S, Schwarz T, Schwarz A,. 2006. Enhanced photocarcinogenesis in interleukin-12-deficient mice. Cancer Res 66: 2962-2969.
133. Mahnke YD, Schirrmacher V,. 2004. Characteristics of a potent tumor vaccine-induced secodary anti-tumor T cell response. Int J Oncol 24: 1427-1434.
134. Major EO,. 2010. Progressive multifocal leukoencephalopathy in patients on immunomodulatory therapies. Annu Rev Med 61: 35-47.
135. Marks F, Furstenberger G, Heinzelman T, Muller-Decker K,. 1995. Mechanism in tumor promotions: guidance for risk assessment and and cancer chemoprevention. Toxicol Lett 82: 907-917.
136. Martin PL,. 2002. Primate models in pharmaceutical drug development. Muenster: Waxman. p 105-118.
137. Martin PL,. 2008. Reproductive toxicity testing for biopharmaceuticals. In:, Cavagnaro JA, editor. Preclinical safety evaluation of biopharmaceuticals. Hoboken, NJ: John Wiley & Son. p 357-377.
138. Martin PL, Bugelski PJ,. 2012. Concordance of preclinical and clinical pharmacology and toxicology of monoclonal antibodies and fusion proteins: soluble targets. Br J Pharmacol 166: 806-822.
139. Martin PL, Oneda S, Treacy G,. 2007. Effects of an anti-TNFα monoclonal antibody, administered throughout pregnancy and lactation, on the development of the macaque immune system. Am J Reprod Immunol 58: 138-149.
140. McCamish M, Woollett G,. 2012. The state of the art in the development of biosimilars. Clin Pharmacol Ther 91: 405-417.
141. McDonnell T, Ioannou Y, Rahman A,. 2014. PEGylated drugs in rheumatology-why develop them and do they work? Rheumatology (Oxford) 53: 391-396.
142. McGonagle D, Aziz A, Dickie LJ, McDermott MF,. 2009. An integrated classification of pediatric inflammatory diseases, based on the concepts of autoinflammation and the immunological disease continuum. Pediatr Res 65: 38R-45R.
143. McInnes EF, Jarrett RF, Langford G, Atkinson C, Horsley J, Goddard MJ, Cozzi E, Schuurman HJ,. 2002. Posttransplant lymphoproliferative disorder associated with primate gamma-herpesvirus in cynomolgus monkeys used in pig-to-primate renal xenotransplantation and primate renal allotransplantation. Transplantation 73: 44-52.
144. Melkus MW, Estes JD, Padgett-Thomas A, Gatlin J, Denton PW, Othieno FA, Wege AK, Haase AT, Garcia JV,. 2006. Humanized mice mount specific adaptive and innate immune responses to EBV and TSST-1. Nat Med 12: 1316-1322.
145. Meno-Tetang GM, Lowe PJ,. 2005. On the prediction of the human response: a recycled mechanistic pharmacokinetic/pharmacodynamic approach. Basic Clin Pharmacol Toxicol 96: 182-192.
146. Miller G,. 1990. EBV. Biology, pathogenesis and medical aspects. In:, Fields BN, Knipe D, editors. Virology, 2nd ed. New York: Raven Press, p 1889-1920.
147. Moloney FJ, de Freitas D, Conlon PJ, Murphy GM,. 2005. Renal transplantation, immunosuppression and the skin: an update. Photodermatol Photoimmunol Photomed 21: 1-8.
148. Mougel F, Dalle S, Balme B, Hounot R, Thomas L,. 2006. Aggressive CD30 large cell lymphoma after cyclosporine given for putative atopic dermatitis. Dermatology 213: 239-241.
149. Muller PY, Brennan FR,. 2009. Safety assessment and dose selection for first-in-human clinical trials with immunomodulatory monoclonal antibodies. Clin Pharmacol Ther 85: 247-258.
150. Muller PY, Milton M, Lloyd P, Sims J, Brennan FR,. 2009. The Minimum Anticipated Biological Effect Level (MABEL) for selection of first human dose in clinical trials with monoclonal antibodies. Curr Opin Biotechnol 20: 1-8.
151. Muyldermans S,. 2013. Nanobodies: natural single-domain antibodies. Annu Rev Biochem 82: 775-797.
152. Müller D, Karle A, Meissburger B, Höfig I, Stork R, Kontermann RE,. 2007. Improved pharmacokinetics of recombinant bispecific antibody molecules by fusion to human serum albumin. J Biol Chem 282: 12650-12660.
153. Müller MR, Saunders K, Grace C, Jin M, Piche-Nicholas N, Steven J, O'Dwyer R, Wu L, Khetemenee L, Vugmeyster Y, et al. 2012. Improving the pharmacokinetic properties of biologics by fusion to an anti-HSA shark VNAR domain. MAbs 4: 673-685.
154. Nam JS, Terabe M, Kang MJ, Chae H, Voong N, Yang YA, Laurence A, Michalowska A, Mamura M, Lonning S, et al. 2008. Transforming growth factor beta
155. Nguyen DH, Hurtado-Ziola N, Gagneux P, Varki A,. 2006. Loss of Siglec expression on T lymphocytes during human evolution. Proc Natl Acad Sci USA 103: 7765-7770.
156. Nimmerjahn F, Ravetch JV,. 2008. Fcγ receptors as regulators of immune responses. Nat Rev Immunol 8: 34-47.
157. Nowicki A, Szenajch J, Ostrowska G, Wojtowicz A, Wojtowicz K, Kruszewski AA, Maruszynski M, Aukerman SL, Wiktor-Jedrzejczak W,. 1996. Impaired tumor growth in colony-stimulating factor 1 (CSF-1)-deficient, macrophage-deficient op/op mouse: evidence for a role of CSF-1-dependent macrophages in formation of tumor stroma. Int J Cancer 65: 112-119.
158. O'Connor A, Rogge M,. 2013. Nonclinical development of a biosimilar: the current landscape. Bioanalysis 5: 537-544.
159. Oganesyan V, Gao C, Shirinian L, Wu H, Dall'Acqua WF,. 2008. Structural characterization of a human Fc fragment engineered for lack of effector function. Acta Crystallogr D Biol Crystallogr 64: 700-704.
160. Orencia. 2007. European public assessment report; scientific discussion, EMEA. Available at http://www.ema.europa.eu%20/humandocs/%20PDFs%20/EPAR/ orencia/H-701-en6.pdf Accessed 8th April, 2014.
161. Pages F, Vives V, Sautes-Fridman C, Fossiez F, Berger A, Cugnenc PH, Tartour E, Fridman WH,. 1999. Control of tumor development by intratumoral cytokines. Immunol Lett 68: 135-139.
162. Penn I,. 1996. Cancers in cyclosporine-treated vs azathioprine-treated patients. Transplant Proc. 28: 876-878.
163. Pentsuk N, van der Laan JW,. 2009. An interspecies comparison of placental antibody transfer-implications for developmental toxicity testing of monoclonal antibodies and for human pregnancy outcome. Birth Defects Res B Dev Reprod Toxicol 86: 328-344.
164. Perry LC, Jones TD, Baker MP,. 2008. New approaches to prediction of immune responses to therapeutic proteins during preclinical development. Drugs R D 9: 385-396.
165. Perry R, Farris G, Bienvenu JG, Dean C Jr, Foley G, Mahrt C, Short B,. 2013. Society of Toxicologic Pathology position paper on best practices on recovery studies: the role of the anatomic pathologist. Toxicol Pathol 41: 1159-1169.
166. Picha KM, Tam SH, Khandekar VS, Soderman AR, Martin EC, Jordan RE, Bugelski PJ,. 2004. Effects of lipopolysaccharide on toxicologically important endpoints in cynomolgus Macaques. Preclinica 2: 427-434.
167. Polson AG, Fuji RN,. 2012. The successes and limitations of preclinical studies in predicting the pharmacodynamics and safety of cell-surface-targeted biological agents in patients. Br J Pharmacol 166: 1600-1602.
168. Ponce R, Abad L, Amaravadi L, Gelzleichter T, Gore E, Green J, Gupta S, Herzyk D, Hurst C, Ivens IA, et al. 2009. Immunogenicity of biologically-derived therapeutics: assessment and interpretation of nonclinical safety studies. Regul Toxicol Pharmacol 54: 164-182.
169. Price KD,. 2010. Bacterial infections in cynomolgus monkeys given small molecule immunomodulatory antagonists. J Immunotoxicol 7: 128-137.
170. Prolia. 2010. FDA pharmacology and toxioclogy summary. Available at http://www.accessdata.fda.gov/drugsatfda-docs/nda%20/2010/125320s000PharmR.pdf Accessed 8th April, 2014.
171. Raptiva. 2009. European Public Assessment Report; Summary of Product Characteristics, EMEA. Available at http://www.ema.europa.eu/docs/en-GB/ document-library/EPAR-Product-Information/human/000542/WC500057853.pdf
172. Reichert JM,. 2013. Antibodies to watch in 2014. MAbs 6: 5-14. [Epub ahead of print].
173. Rennert PD, Browning JL, Hochman PS,. 1997. Selective disruption of ligands reveals a novel set of mucosal lymph nodes ad unique effects on lymph node cellular organization. Int Immunol 11: 1627-1639.
174. Richter G, Krüger-Krasagakes S, Hein G, Hüls C, Schmitt E, Diamantstein T, Blankenstein T,. 1993. Interleukin 10 transfected into Chinese hamster ovary cells prevents tumor growth and macrophage infiltration. Cancer Res 53: 4134-4137.
175. Riley JK, Yokoyama WM,. 2008. NK cell tolerance and the materno-fetal interface. Am J Reprod Immunol 59: 371-387.
176. RoActemra. 2013. EMA. European Public Assessment Report. Summary of Product Characteristics. Available at http://www.ema.europa.eu/docs/en-GB/ document-library/EPAR-Summary-for-the-public/human/000955/WC500054886.pdf Accessed 8th April, 2008.
177. Roberts SA, Andrews PA, Blanset D, Flagella KM, Gorovits B, Lynch CM, Martin PL, Kramer-Stickland K, Thibault S, Warner G,. 2013. Considerations for the nonclinical safety evaluation of antibody drug conjugates for oncology. Regul Toxicol Pharmacol 67: 382-391.
178. Rogers KA, Scinicariello F, Attanasio R,. 2006. IgG Fc receptor III homologues in nonhuman primate species: genetic characterization and ligand interactions. J Immunol 177: 3848-3856.
179. Roopenian DC, Akilesh S,. 2007. FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol 7: 715-725.
180. Rosenblum H, Amital H,. 2011. Anti-TNF therapy: safety aspects of taking the risk. Autoimmun Rev 10: 563-568.
181. Roux S, Sablé E, Porsolt RD,. 2005. Primary observation (Irwin) test in rodents for assessing acute toxicity of a test agent and its effects on behavior and physiological function. Curr Protoc Pharmacol. 2005 Jan 1; Chapter 10: Unit 10.10. doi: 10.1002/0471141755.ph1010s27.
182. Rutgeerts P, Van Assche G, Vermeire S,. 2004. Optimizing anti-TNF treatment in inflammatory bowel disease. Gastroenterology 126: 1593-1610.
183. Ryan AM, Eppler DB, Hagler KE, Bruner RH, Thomford P, Hall J, Shopp RL, O'Neil CA,. 1999. Preclinical safety evaluation of rhuMabVEGF, an antiangiogenic humanized monoclonal antibody. Toxicol Pathol 27: 78-86.
184. th October, 2013.
185. Ryffel B, Mihatsch MJ, Fisher GL,. 1992. Immunosuppression and cancer: the ciclosporine case. Drug Chem Toxicol 15: 95-115.
186. Salliot C, Dougados M, Gossec L,. 2009. Risk of serious infections during rituximab, abatacept and anakinra treatments for rheumatoid arthritis: meta-analyses of randomised placebp-controlled trials. Ann Rheum Dis 68: 25-32.
187. Santostefano MJ, Kirchner J, Vissinga C, Fort M, Lear S, Pan WJ, Prince PJ, Hensley KM, Tran D, Rock D, et al. 2012. Off-target platelet activation in macaques unique to a therapeutic monoclonal antibody. Toxicol Pathol 40: 899-917.
188. Scolnik PA,. 2009. mAbs: a business perspective. MAbs 1: 179-184.
189. Simister NE,. 2003. Placental transfer of immunoglobulin G. Vaccine 21: 3365-3369.
190. Simon TA, Smitten AL, Franklin J, Askling J, Lacaille D, Wolfe F, Hochberg MC, Qi K, Suissa S,. 2009. Malignancies in the rheumatoid arthritis abatacept clinical development program: an epidemiological assessment. Ann Rheum Dis 68: 1819-1826.
191. Simulect. 1998. EMA. European Public Assessment Report; scientific discussion. Available at http://www.ema.europa.eu/docs/en-GB/document-library/ EPAR-Scientific-Discussion/human/000207/WC500053538.pdf Accessed 8th April, 2014.
192. Smolec J, DeSilva B, Smith W, Weiner R, Kelly M, Lee B, Khan M, Tacey R, Hill H, Celniker A, et al. 2005. Bioanalytical method validation for macromolecules in support of pharmacokinetic studies. Pharm Res 22: 1425-1431.
193. Soliris. 2007. FDA. Pharmacology/Toxicology Review and Evaluation. Available at http://www.accessdata.fda.gov/drugsatfda-docs/nda/2007/125166s0000- PharmR.pdf Accessed 8th April, 2008.
194. Stelara. 2009. FDA. Pharmacology and toxicology summary. Available at http://www.accessdata.fda.gov/drugsatfda-docs/nda%20/2009/125261 s000-%20PharmR.pdf Accessed 8th April, 2014.
195. Stevison LS, Kohn MH,. 2008. Determining genetic background in captive stocks of cynomolgus macaques (Macaca fascicularis). J Med Primatol 37: 311-317.
196. Stewart J,. 2009. Developmental toxicity testing of monoclonal antibodies: an enhanced pre- and post-natal study design option. Reprod Toxicol 28: 220-225.
197. Straus SE, Cohen JI, Tosato G, Meier J,. 1993. EBV infections: biology, pathogensis and management. Ann Intern Med 118: 45-58.
198. Strowig T, Gurer C, Ploss A, Liu Y-F, Arrey F, Sashihara J, Koo G, Rice CM, Young JW, Chadburn A, et al. 2009. Priming of protective T cell responses against virus-induced tumors in mice with human immune system components. J Exp Med 206: 1423-1434.
199. Stubenrauch K, Wessels U, Birnboeck H, Ramirez F, Jahreis A, Schleypen J,. 2010. Subset analysis of patients experiencing clinical events of a potentially immunogenic nature in the pivotal clinical trials of tocilizumab for rheumatoid arthritis: evaluation of an antidrug antibody ELISA using clinical adverse event driven immunogenicity testing. Clin Ther 32: 1597-1609.
200. Stüve O, Marra CM, Jerome KR, Cook L, Cravens PD, Cepok S, Frohman EM, Phillips JT, Arendt G, Hemmer B, et al. 2006. Immune surveillance in multiple sclerosis patients treated with natalizumab. Ann Neurol 59: 743-747.
201. Subramanyam M, Rinaldi N, Mertsching E, Hutto D,. 2008. Selection of relevant species. In:, Cavagnaro JA, editor. Preclinical safety evaluation of biopharmaceuticals. Hoboken, NJ: John Wiley & Son. p 181-206-240.
202. Sunil-Chandra NP, Arno J, Fazakerley J, Nash AA,. 1994. Lymphoprolifertive disease in mice infected with gammaherpesvirus 68. Am J Pathol 145: 818-826.
203. Suntharalingam G, Perry MR, Ward S, Brett SJ, Castello-Cortes A, Brunner MD, Panoskaltsis N,. 2006. Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N Engl J Med 355: 1018-1028.
204. Swinnen LJ, Costanzo-Nordin MR, Fisher SG, O'Sullivan EJ, Johnson MR, Heroux AL, Dizikes GJ, Pifarre R, Fisher RI,. 1990. Increased incidence of lymphoproliferative disorder after immunosuppression with the monoclonal antibody OKT3 in cardiac-transplant recipients. N Engl J Med 323: 1723-1728.
205. Szekeres-Bartho J,. 2002. Immunological relationship between the mother and fetus. Int Rev Immunol 21: 471-495.
206. Takaoka M, Sehata S, Maejima T, Imai T, Torii M, Satoh H, Toyosawa K, Tanakamaru ZY, Adachi T, Hisada S, et al. 2003. Interlaboratory comparison of short-term carcinogenicity studies using CB6F1-rasH2 transgenic mice. Toxicol Pathol 31: 191-199.
207. Tibbitts J, Cavagnaro JA, Haller CA, Marafino B, Andrews PA, Sullivan JT,. 2010. Practical approaches to dose selection for first-in-human clinical trials with novel biopharmaceuticals. Regul Toxicol Pharmacol 58: 243-251.
208. Trapnell BC, Carey BC, Uchida K, Suzuki T,. 2009. Pulmonary alveolar proteinosis, a primary immunodeficiency of impaired GM-CSF stimulation of macrophages. Curr Opin Immunol 21: 514-521.
209. Treacy G,. 2000. Using an analogous monoclonal antibody to evaluate the reproductive and chronic toxicity potential for a humanized anti-TNF-α monoclonal antibody. Hum Exp Toxicol 19: 226-229.
210. Tysabri. 2004. Toxicology summary. Available at: http://www.accessdata. fda.gov/drugsatfda-docs/nda/2004/125104 s000-%20Natalizumab-Pharmr-P1.pdf Accessed 8th April, 2014.
211. Vahle JL, Finch GL, Heidel SM, Hovland DN Jr, Ivens I, Parker S, Ponce RA, Sachs C, Steigerwalt R, Short B, et al. 2010. Carcinogenicity assessment of biotechnology-derived pharmaceuticals: a review of approved molecules and best practice recommendations. Toxicol Pathol 38: 522-553.
212. Vaidyanathan A, McKeever K, Anand B, Eppler S, Weinbauer GF, Beyer JC,. 2011. Developmental imunotoxicology assessment of rituximab in cynomolgus monkeys. Toxicol Sci 119: 116-125.
213. Vargas HM, Amouzadeh HR, Engwall MJ,. 2013. Nonclinical strategy considerations for safety pharmacology: evaluation of biopharmaceuticals. Expert Opin Drug Saf 12: 91-102.
214. Vultaggio A, Marucci A, Nencini F, Pratesi S, Parronchi P, Rossi O, Romagnani S, Maggi E,. 2010. Anti-infliximab IgE and non-lgE antibodies and induction of infusion-related severe anaphylactic reactions. Allergy 65: 657-661.
215. Wadhwa M, Gaines-Das R, Thorpe R, Mire-Sluis A,. 2005. Detection, measurement and characterization of unwanted antibodies induced by therapeutic biologicals. Dev Biol (Basel) 122: 155-170.
216. Walker M, Makropoulos D, Achuthanandam R, Bugelski P,. 2010. Recent advances in the understanding of drug-mediated infusion reactions and cytokine release syndrome. Curr Opin Drug Discov Devel 13: 124-135.
217. Warncke M, Calzascia T, Coulot M, Balke N, Touil R, Kolbinger F, Heusser C,. 2012. Different adaptations of IgG effector function in human and nonhuman primates and implications for therapeutic antibody treatment. J Immunol 188: 4405-4411.
218. Weinbauer GF, Luft J, Fuchs A,. 2013. The enhanced pre- and postnatal development study for monoclonal antibodies. Methods Mol Biol 947: 185-200.
219. Wetter DA, Davis MD,. 2009. Lupus-like syndrome attributable to anti-tumor necrosis factor alpha therapy in 14 patients during an 8-year period at the Mayo Clinic. Mayo Clin Proc 84: 979-984.
220. Wiczling P, Rosenweig M, Vaickus L, Jusko WJ,. 2009. Pharmacokinetics and pharmacodymaics of a chimeric/humanized anri-CD3 monoclonal antibody, otelixizumab (TRX4), in subjects with psoriasis and with type 1 diabetes mellitus. J Clin Pharmacol 50: 494-506.
221. Wierda WG, Kipps TJ, Mayer J, Stilgenbauer S, Williams CD, Hellmann A, Robak T, Furman RR, Hillmen P, Trneny M, et al. 2010. Oftumumab as a single-agent CD20 immunotherapy in fludarabine-refractory chronic lymphocytic leukemia. J Clin Oncol 28: 1749-1755.
222. Wing M,. 2008. Monoclonal antibody first dose cytokine release syndromes-mechanisms and prediction. J Immunotoxicol 5: 11-15.
223. Wislez M, Rabbe N, Marchal J, Milleron B, Crestani B, Mayaud C, Antoine M, Soler P, Cadranel J,. 2003. Hepatocyte growth factor production by neutrophils infiltrating bronchioloalveolar subtype pulmonary adenocarcinoma: role in tumor progression and death. Cancer Res 63: 1405-1412.
224. Xiao M, Wang C, Zhang J, Li Z, Zhao X, Qin Z,. 2009. IFNgamma promotes papilloma development by up-regulating Th17-associated inflammation. Cancer Res 69: 2010-2017.
225. Xolair. 2005. EMA. European public assessment report scientifc discussion. Available at: http://www.ema.europa.eu/docs/en%20-GB/document- library/EPAR-Scientific-Discussion/human/000606/WC500057295.pdf Accessed 8th April, 2014.
226. Yabu K, Warty VS, Gorelik E, Shinozuka H,. 1991. Cyclosporin promotes the induction of thymic lymphomas in C57BL/6 mice irradiated by a single dose of gamma-radiation. Carcinogenesis 12: 43-46.
227. Yamawaki M, Katiyar SK, Anderson CY, Tubesing KA, Mukhtar H, Elmets CA,. 1997. Genetic variation in the low-dose UV-induced suppression of contact hypersensitivity and in the skin photocarcinogenesis response. J Invest Dermatol 109: 716-721.
228. Zenapax. 1997. FDA. Labelling Text. Available at http://www.fda.gov/ downloads/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/ approvalapplications/therapeuticbiologicapplications/ucm113468.pdf Accessed 8th April, 2008.
229. Zhu X, Mulcahy LA, Mohammed RA, Lee AH, Franks HA, Kilpatrick L, Yilmazer A, Paish EC, Ellis IO, Patel PM, Jackson AM,. 2008. AMIL-17 expression by breast-cancer-associated macrophages: IL-17 promotes invasiveness of breast cancer cell lines. Breast Cancer Res 10: R95.