Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-8448b6f56d-wq2xx Total loading time: 0 Render date: 2024-04-19T19:46:01.170Z Has data issue: false hasContentIssue false

2 - Immunogenicity Assessment of Antibody Therapeutics

from PART I - HUMANIZED ANTIBODIES

Published online by Cambridge University Press:  15 December 2009

By
Philippe Stas ,
Jurgen Pletinckx ,
Yannick Gansemans  and
Ignace Lasters
Edited by
Melvyn Little
Melvyn Little
Affiliation:
Affimed Therapeutics AG
Get access

Summary

With over 20 therapeutic antibodies currently approved by the Food and Drug Administration (FDA) and close to 100 leads in clinical trials, therapeutic antibodies are responsible for a considerable part of the therapeutic proteins sales worldwide. The observation of immunogenicity with the early therapeutic antibodies did not come as a surprise, as many of them were murine antibodies or chimeric variants, consisting of murine variable parts in conjunction with a human constant domain. Over time, there has been a strong evolution toward the development of humanized and fully human antibodies, thereby reducing the observed immunogenicity to a significant extent. General side effects such as anaphylaxis and allergy against protein therapeutics are also less prevalent but this is due to better manufacturing processes giving more homogeneous products.

However, some of the currently available fully human antibodies have induced significant immunogenic responses over time. This has led to the regulatory instances in Europe and the United States supporting the development of guidelines to assess the likelihood of observing immunogenicity and its potential severity and side effects.

IMMUNOGENICITY DRIVERS

Several factors contribute to the potential immunogenicity of a protein therapeutic:

  • Homology to human or endogenous proteins: The degree of “foreignness” of a protein to the host is one of the major contributors to an immune response. Indeed, the likelihood to observe immunogenicity related to a bacterium-derived protein therapeutic, such as staphylokinase, is higher than against proteins that show high homology to endogenous proteins, such as erythropoietin (EPO) and insulin. The overall immunogenicity of antibody therapeutics has been severely reduced by the development of fully human and humanized therapeutic antibodies as compared to the first-generation murine and chimeric antibodies (Hwang and Foote, 2005).

  • […]

Type
Chapter
Information
Recombinant Antibodies for Immunotherapy , pp. 20 - 42
Publisher: Cambridge University Press
Print publication year: 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Anthony, DD and Lehmann, PV. T-cell epitope mapping using the ELISPOT approach. Methods 2003; 29:260–269.CrossRefGoogle ScholarPubMed
Bachmann, MF, Rohrer, UH, Kundig, TM, Burki, K, Hengartner, H, and Zinkernagel, RM. The influence of antigen organization on B cell responsiveness. Science 1993; 262:1448–1451.CrossRefGoogle ScholarPubMed
Baert, F, Noman, M, Vermeire, S, Assche, G, D' Haens, G, Carbonez, A, and Rutgeerts, P. Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease. N Engl J Med 2003; 348:601–608.CrossRefGoogle ScholarPubMed
Bearden, CM, Book, BK, Sidner, RA, and Pescovitz, MD. Removal of therapeutic anti-lymphocyte antibodies from human sera prior to anti-human leukocyte antibody testing. J Immunol Methods 2005; 300:192–199.CrossRefGoogle ScholarPubMed
Bender, NK, Heilig, CE, Dröll, B, Wohlgemuth, J, Armbruster, FP, and Heilig, B. Immunogenicity, efficacy and adverse events of adalimumab in RA patients. Rheumatol Int 2007; 27:269–274.CrossRefGoogle ScholarPubMed
Boeckh, M, Berrey, MM, Bowden, RA, Crawford, SW, Balsley, J, and Corey, L. Phase 1 evaluation of the respiratory syncytial virus-specific monoclonal antibody palivizumab in recipients of hematopoietic stem cell transplants. J Infect Dis 2001; 184:350–354.CrossRefGoogle ScholarPubMed
Börjesson, PK, Postema, EJ, Roos, JC, Colnot, DR, Marres, HA, Schie, MH, Stehle, G, Bree, R, Snow, GB, Oyen, WJ, et al. Phase I therapy study with 186Re-labeled humanized monoclonal antibody BIWA 4 (bivatuzumab) in patients with head and neck squamous cell carcinoma. Clin Cancer Res 2003; 9:3961s–3972s.Google Scholar
Borrás-Cuesta, F, Golvano, J, García-Granero, M, Sarobe, P, Riezu-Boj, J, Huarte, E, and Lasarte, J. Specific and general HLA-DR binding motifs: comparison of algorithms. Hum Immunol 2000; 61:266–278.CrossRefGoogle ScholarPubMed
Bowen, JD, Petersdorf, SH, Richards, TL, Maravilla, KR, Dale, DC, Price, TH, St John, TP, and Yu, AS. Phase I study of a humanised anti-CD11/CD18 monoclonal antibody in multiple sclerosis. Clin Pharmacol Ther 1998; 64:339–346.CrossRefGoogle Scholar
Busse, W, Corren, J, Lanier, BQ, McAlary, M, Fowler-Taylor, A, Cioppa, GD, As, A, Gupta, N. Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol 2001; 108:184–190.CrossRefGoogle ScholarPubMed
Carpenter, PA, Appelbaum, FR, Corey, L, Deeg, HJ, Doney, K, Gooley, T, Krueger, J, Martin, P, Pavlovic, S, Sanders, J, et al. A humanised non-FcR-binding anti-CD3 antibody, visilizumab, for treatment of steroid-refractory acute graft-versus-host disease. Blood 2002; 99:2712–2719.CrossRefGoogle Scholar
Casadevall, N, Nataf, J, Viron, B, Kolta, A, Kiladjian, JJ, Martin-Dupont, P, Michaud, P, Papo, T, Ugo, V, Teyssandier, I, Varet, B, and Mayeux, P. Pure red-cell aplasia and antierythropoietin antibodies in patients treated with recombinant erythropoietin. N Engl J Med 2002; 346(7):469–475.CrossRefGoogle ScholarPubMed
Castellino, F, Zhong, G, and Germain, RN. Antigen presentation by MHC class II molecules: invariant chain function, protein trafficking, and the molecular basis of diverse determinant capture. Hum Immunol 1997; 54:159–169.CrossRefGoogle ScholarPubMed
Chicz, RM, Urban, RG, Lane, WS, Gorga, JC, Stern, LJ, Vignali, DA, and Strominger, JL. Predominant naturally processed peptides bound to HLA-DR1 are derived from MHC-related molecules and are heterogeneous in size. Nature 1992; 358:764–768.CrossRefGoogle ScholarPubMed
Choy, EHS, Schantz, A, Pitzalis, C, Kingsley, GH, and Panayi, GS. The pharmacokinetics and human anti-mouse antibody response in rheumatoid arthritis patients treated with a chimeric anti-CD4 monoclonal antibody. Br J Rheumatol 1998; 37:801–802.CrossRefGoogle ScholarPubMed
Colnot, DR, Roos, JC, Bree, R, Wilhelm, AJ, Kummer, JA, Hanft, G, Heider, KH, Stehle, G, Snow, GB, and Dongen, GA. Safety, biodistribution, pharmacokinetics, and immunogenicity of 99mTc-labeled humanised monoclonal antibody BIWA 4 (bivatuzumab) in patients with squamous cell carcinoma of the head and neck. Cancer Immunol Immunother 2003; 52:576–582.CrossRefGoogle Scholar
Davenport, MP, Smith, KJ, Barouch, D, Reid, SW, Bodnar, WM, Willis, AC, Hunt, DF, and Hill, AV. HLA Class I binding motifs derived from random peptide libraries differ at the COOH terminus from those of eluted peptides. J Exp Med 1997; 185:367–371.CrossRefGoogle Scholar
Davies, MN, Sansom, CE, Beazley, C, and Moss, DS. A novel predictive technique for the MHC class II peptide-binding interaction. Mol Med 2003; 9:220–225.CrossRefGoogle ScholarPubMed
Davis, MM and Bjorkman, PJ. T-cell antigen receptor genes and T-cell recognition. Nature 1988; 334:395–402.CrossRefGoogle ScholarPubMed
Davis, TA, Grillo-López, AJ, White, CA, McLaughlin, P, Czuczman, MS, Link, BK, Maloney, DG, Weaver, RL, Rosenberg, J, and Levy, R. Rituximab anti-CD20 monoclonal antibody therapy in non-Hodgkin's lymphoma: safety and efficacy of re-treatment. J Clin Oncol 2000; 18:3135–3143.CrossRefGoogle ScholarPubMed
Desmet, J, Meersseman, G, Boutonnet, N, Pletinckx, J, Clercq, K, Debulpaep, M, Braeckman, T, and Lasters, I. Anchor profiles of HLA-specific peptides: analysis by a novel affinity scoring method and experimental validation. Proteins 2005; 58:53–69.CrossRefGoogle ScholarPubMed
Djukanović, R, Wilson, SJ, Kraft, M, Jarjour, NN, Steel, M, Chung, KF, Bao, W, Fowler-Taylor, A, Matthews, J, Busse, WW, Holgate, ST, and Fahy, JV. Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma. Am J Resp Crit Care Medicine, 2005; 170, 583–593.CrossRefGoogle Scholar
,European Agency for the Evaluation of Medicinal Products (EMEA) Guideline on immunogenicity assessment of biotechnology-derived therapeutic proteins. EMEA/CHMP/BMWP/14327/2006, draft 2007.
Eng, JK, McCormack, AL, and Yates, JR. An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database. J Am Soc Mass Spectrom 1994; 5: 976–989.CrossRefGoogle Scholar
Falk, K, Roetzschke, O, Stefanovic, S, Jung, G, and Rammensee, HG. Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature 1991; 351:290–296.CrossRefGoogle ScholarPubMed
Feagan, BG, Greenberg, GR, Wild, G, Fedorak, RN, Paré, P, McDonald, JW, Dubé, R, Cohen, A, Steinhart, AH, Landau, S, et al. Treatment of ulcerative colitis with a humanised antibody to the alpha4beta7 integrin. N Engl J Med 2005; 352:2499–2507.CrossRefGoogle Scholar
Ghosh, S, Goldin, E, Gordon, FH, Malchow, HA, Rask-Madsen, J, Rutgeerts, P, Vyhnálek, P, Zádorová, Z, Palmer, T, Donoghue, S, et al. Natalizumab for active Crohn's disease. N Engl J Med 2003; 348:24–32.CrossRefGoogle ScholarPubMed
Goldstein, G, Fuccello, AJ, Norman, DJ, Shield, CF, Colvin, RB, and Cosimi, AB. OKT3 monoclonal antibody plasma levels during therapy and the subsequent development of host antibodies to OKT3. Transplantation 1986; 42:507–511.CrossRefGoogle ScholarPubMed
Gordon, MS, Margolin, K, Talpaz, M, Sledge, GW, Holmgren, E, Benjamin, R, Stalter, S, Shak, S, and Adelman, D. Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. J Clin Oncol 2001; 19:843–850.CrossRefGoogle ScholarPubMed
Gulukota, K, Sidney, J, Sette, A, and DeLisi, C. Two complementary methods for predicting peptides binding major histocompatibility complex molecules. J Mol Biol 1997; 267:1258–1267.CrossRefGoogle ScholarPubMed
Gutheil, JC, Campbell, TN, Pierce, PR, Watkins, JD, Huse, WD, Bodkin, DJ, and Cheresh, DA. Targeted antiangiogenic therapy for cancer using Vitaxin: a humanized monoclonal antibody to the integrin alphavbeta3. Clin Cancer Res 2000; 6:3056–3061.Google ScholarPubMed
Hammer, J, Bono, E, Gallazzi, F, Belunis, C, Nagy, Z, and Sinigaglia, F. Precise prediction of major histocompatibility complex class II-peptide interaction based on peptide side chain scanning. J Exp Med 1994; 180:2353–2358.CrossRefGoogle ScholarPubMed
Hanauer, SB. Review article: safety of infliximab in clinical trials. Aliment Pharmacol Ther 1999; 13:16–22.CrossRefGoogle ScholarPubMed
Hanauer, SB, Feagan, BG, Lichtenstein, GR, Mayer, LF, Schreiber, S, Colombel, JF, Rachmilewitz, D, Wolf, DC, Olson, A, Bao, W, et al. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet 2002; 359:1541–1549.CrossRefGoogle ScholarPubMed
Handgretinger, R, Anderson, K, Lang, P, Dopfer, R, Klingebiel, T, Schrappe, M, Reuland, P, Gillies, SD, Reisfeld, RA, and Neithammer, D. A phase I study of human/mouse chimeric antiganglioside GD2 antibody ch14.18 in patients with neuroblastoma. Eur J Cancer 1995; 31A:261–267.CrossRefGoogle ScholarPubMed
Harding, F. CD4+ T cell epitope identification: applications to allergy. Clin Exp Allergy 2003; 33: 557–565.CrossRefGoogle ScholarPubMed
Hillmen, P, Young, NS, Schubert, J, Brodsky, RA, Socié, G, Muus, P, Röth, A, Szer, J, Elebute, MO, Nakamura, R, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med 2006; 355; 1233–1243.CrossRefGoogle ScholarPubMed
Hunt, DF, Michel, H, Dickinson, TA, Shabanowitz, J, Cox, AL, Sakaguchi, K, Appella, E, Grey, HM, and Sette, A. Peptides presented to the immune system by the murine class II major histocompatibility complex molecule I-Ad. Science 1992; 256:1817–1820.CrossRefGoogle ScholarPubMed
Hwang, W and Foote, J. Immunogenicity of engineered antibodies. Methods 2005; 36:3–10.CrossRefGoogle ScholarPubMed
Isaacs, JD, Manna, VK, Rapson, N, Bulpitt, KJ, Hazleman, BL, Matteson, EL, St Clair, EW, Schnitzer, TJ, and Johnston, JM. CAMPATH-1H in rheumatoid arthritis – an intravenous dose-ranging study. Br J Rheumatol 1996a; 35:231–240.CrossRefGoogle ScholarPubMed
Isaacs, JD, Watts, RA, Hazleman, BL, Hale, G, Keogan, MT, Cobbold, SP, and Waldmann, H. Humanised monoclonal antibody therapy for rheumatoid arthritis. Lancet 1992; 340:748–752.CrossRefGoogle ScholarPubMed
Isaacs, JD, Wing, MG, Greenwood, JD, Hazleman, BL, Hale, G, and Waldmann, H. A therapeutic human IgG4 monoclonal antibody that depletes target cells in humans. Clin Exp Immunol 1996b; 106:427–433.CrossRefGoogle ScholarPubMed
Jurcic, JG, DeBlasio, T, Dumont, L, Yao, TJ, and Scheinberg, DA. Molecular remission induction with retinoic acid and anti-CD33 monoclonal antibody HuM195 in acute promyelocytic leukemia. Clin Cancer Res 2000; 6:372–380.Google ScholarPubMed
Kaminski, MS, Zelenetz, AD, Press, OW, Saleh, M, Leonard, J, Fehrenbacher, L, Lister, TA, Stagg, RJ, Tidmarsh, GF, Kroll, S, et al. Pivotal study of iodine I 131 tositumomab for chemotherapy-refractory low-grade or transformed low-grade B-cell non-Hodgkin's lymphomas. J Clin Oncol 2001; 19:3918–3928.CrossRefGoogle ScholarPubMed
Keystone, EC, Kavanaugh, AF, Sharp, JT, Tannenbaum, H, Hua, Y, Teoh, LS, Fischkoff, SA, and Chartash, EK. Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial. Arthritis Rheum 2004; 50:1400–1411.CrossRefGoogle ScholarPubMed
Koren, E. From characterization of antibodies to prediction of immunogenicity. Dev Biol 2002; 109:87–95.Google ScholarPubMed
Kovarik, J, Wolf, P, Cisterne, JM, Mourad, G, Lebranchu, Y, Lang, P, Bourbigot, B, Cantarovich, D, Girault, D, Gerbeau, C, Schmidt, AG, and Soulillou, JP. Disposition of basiliximab, an interleukin-2 receptor monoclonal antibody, in recipients of mismatched cadaver renal allografts. Transplantation 1997; 64:1701–1705.CrossRefGoogle ScholarPubMed
Kramer, EL, Liebes, L, Wasserheit, C, Noz, ME, Blank, EW, Zabalegui, A, Melamed, J, Furmanski, P, Peterson, JA, and Ceriani, RL. Initial clinical evaluation of radiolabeled MX-DTPA humanized BrE-3 antibody in patients with advanced breast cancer. Clin Cancer Res 1998; 4:1679–1688.Google ScholarPubMed
Kropshofer, H, Hämmerling, GJ, and Vogt, AB. The impact of the non-classical MHC proteins HLA-DM and HLA-DO on loading of MHC class II molecules. Immunol Rev 1999; 172:267–278.CrossRefGoogle ScholarPubMed
Lipsky, PE, Heijde, DM, St Clair, EW, Furst, , Breedveld, FC, Kalden, JR, Smolen, JS, Weisman, M, Emery, P, Feldmann, M, et al. Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. N Engl J Med 2000; 343:1594–1602.CrossRefGoogle ScholarPubMed
Looney, RJ, Anolik, JH, Campbell, D, Felgar, RE, Young, F, Arend, LJ, Sloand, JA, Rosenblatt, J, and Sanz, I. B cell depletion as a novel treatment for systemic lupus erythematosus: a phase I/II dose-escalation trial of rituximab. Arthritis Rheum 2004; 50:2580–2589.CrossRefGoogle ScholarPubMed
Maini, RN, Breedveld, FC, Kalden, JR, Smolen, JS, Davis, D, Macfarlane, JD, Antoni, C, Leeb, B, Elliott, MJ, Woody, JN, et al. Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis Rheum 1998; 41:1552–1563.3.0.CO;2-W>CrossRefGoogle ScholarPubMed
Mamitsuka, H. Predicting peptides that bind to MHC molecules using supervised learning of Hidden Markov Models. Proteins 1998; 33:460–474.3.0.CO;2-M>CrossRefGoogle ScholarPubMed
Margolin, K, Gordon, MS, Holmgren, E, Gaudreault, J, Novotny, W, Fyfe, G, Adelman, D, Stalter, S, and Breed, J. Phase Ib trial of intravenous recombinant humanized monoclonal antibody to vascular endothelial growth factor in combination with chemotherapy in patients with advanced cancer: pharmacologic and long-term safety data. J Clin Oncol 2001; 19:851–856.CrossRefGoogle ScholarPubMed
Martin, W, Sbai, H, and Groot, AS. Bioinformatics tools for identifying class I-restricted epitopes. Methods, March 2003, 29(3): 289–298.CrossRefGoogle ScholarPubMed
McClung, MR, Lewiecki, EM, Cohen, SB, Bolognese, MA, Woodson, GC, Moffett, AH, Peacock, M, Miller, PD, Lederman, SN, Chesnut, CH, et al. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 2006; 354:821–831.CrossRefGoogle ScholarPubMed
McFarland, BJ and Beeson, C. Binding interactions between peptides and proteins of the class II major histocompatibility complex. Med Res Rev 2002; 22:168–203.CrossRefGoogle ScholarPubMed
McIntyre, JA, Kincade, M, and Higgins, NG. Detection of IGA anti-OKT3 antibodies in OKT3-treated transplant recipients. Transplantation 1996; 61:1465–1469.CrossRefGoogle ScholarPubMed
Menter, A, Gordon, K, Carey, W, Hamilton, T, Glazer, S, Caro, I, Li, N, and Gulliver, W. Efficacy and safety observed during 24 weeks of efalizumab therapy in patients with moderate to severe plaque psoriasis. Arch Dermatol 2005; 141:31–38.CrossRefGoogle ScholarPubMed
Milik, M, Sauer, D, Brunmark, AP, Yuan, L, Vitiello, A, Jackson, MR, Peterson, PA, Skolnick, J, and Glass, CA. Application of an artificial neural network to predict specific class I MHC binding peptide sequences. Nat Biotechnol 1998; 16:753–756.CrossRefGoogle ScholarPubMed
Mire-Sluis, AR, Barrett, YC, Devanarayan, V, Koren, E, Liu, H, Maia, M, Parish, T, Scott, G, Shankar, G, Shores, E, et al. Recommendations for the design and optimization of immunoassays used in the detection of host antibodies against biotechnology products. J Immunol Methods 2004; 289:1–16.CrossRefGoogle ScholarPubMed
Østensen, M, Sicher, P, Forger, F, and Villiger, PM. Activation markers of peripheral blood mononuclear cells in late pregnancy and after delivery: a pilot study. Ann Rheum Dis 2005; 64:318–320.CrossRefGoogle Scholar
Papp, KA, Miller, B, Gordon, KB, Caro, I, Kwon, P, Compton, PG, Leonardi, CL, and Efalizumab Study Group. Efalizumab retreatment in patients with moderate to severe chronic plaque psoriasis. J Am Acad Dermatol 2006; 54:S164–S170.CrossRefGoogle Scholar
Patton, A, Mullenix, MC, Swanson, SJ, and Koren, E. An acid dissociation bridging ELISA for detection of antibodies directed against therapeutic proteins in the presence of antigen. J Immunol Methods 2005; 304:189–195.CrossRefGoogle ScholarPubMed
Peters, B and Sette, A: Generating quantitative models describing the sequence specificity of biological processes with the stabilized matrix method. BMCBioinformatics 2005; 6:132.Google Scholar
Peters, B, Tong, W, Sidney, J, Sette, A, and Weng, Z. Examining the independent binding assumption for binding of peptide epitopes to MHC-I molecules. Bioinformatics 2003; 19:1765–1772.CrossRefGoogle ScholarPubMed
Pijpe, J, Imhoff, GW, Spijkervet, FK, Roodenburg, JL, Wolbink, GJ, Mansour, K, Vissink, A, Kallenberg, CG, and Bootsma, H. Rituximab treatment in patients with primary Sjögren's syndrome: an open-label phase II study. Arthritis Rheum 2005 52:2740–2750.CrossRefGoogle ScholarPubMed
Piro, LD, White, CA, Grillo-López, AJ, Janakiraman, N, Saven, A, Beck, TM, Varns, C, Shuey, S, Czuczman, M, Lynch, JW, et al. Extended Rituximab (anti-CD20 monoclonal antibody) therapy for relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma. Ann Oncol 1999; 10:655–661.CrossRefGoogle ScholarPubMed
Present, DH, Rutgeerts, P, Targan, S, Hanauer, SB, Mayer, L, Hogezand, RA, Podolsky, DK, Sands, BE, Braakman, T, DeWoody, KL, et al. Infliximab for the treatment of fistulas in patients with Crohn's disease. N Engl J Med 1999; 340:1398–1405.CrossRefGoogle ScholarPubMed
Rammensee, H, Bachmann, J, Emmerich, NP, Bachor, OA, and Stevanovic, S. SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics 1999; 50:213–219.CrossRefGoogle ScholarPubMed
Reche, PA, Glutting, JP, Zhang, H, and Reinherz, EL. Enhancement to the RANKPEP resource for the prediction of peptide binding to MHC molecules using profiles. Immunogenetics 2004; 56: 405–419.CrossRefGoogle ScholarPubMed
Reiff, A. A review of Campath in autoimmune disease: biologic therapy in the gray zone between immunosuppression and immunoablation. Hematology 2005; 10:79–93.CrossRefGoogle ScholarPubMed
Ritter, G, Cohen, LS, Williams, C Jr, Richards, EC, Old, LJ, and Welt, S. Serological analysis of human anti-human antibody responses in colon cancer patients treated with repeated doses of humanised monoclonal antibody A33. Cancer Res 2001; 61:6851–6859.Google Scholar
Rosenberg, AS. Effects of protein aggregates: an immunologic perspective. AAPS J 2006; 8:E501–E507.CrossRefGoogle Scholar
Rosenberg, AS and Worobec, A. A risk-based approach to immunogenicity concerns of therapeutic protein products – Part 1 – considering consequences of the immune response to a protein. Biopharm Int 2004a; 17:22–26.Google Scholar
Rosenberg, AS and Worobec, A. A risk-based approach to immunogenicity concerns of therapeutic protein products – Part 2 – considering host-specific and product-specific factors impacting immunogenicity. Biopharm Int 2004b; 17:34–42.Google Scholar
Rosenberg, AS and Worobec, A. A risk-based approach to immunogenicity concerns of therapeutic protein products – Part 3 – effects of manufacturing changes in immunogenicity and the utility of animal immunogenicity studies. Biopharm Int 2005; 18:32–36.Google Scholar
Rudensky, AY, Preston-Hurlburt, P, Hong, SC, Barlow, A, and Janeway, CA. Sequence analysis of peptides bound to MHC class II molecules. Nature 1991; 353:622–627.CrossRefGoogle ScholarPubMed
Rudolf, MP, Man, S, Melief, CJM, Sette, A, and Kast, WM. Human T-cell responses to HLA-A-restricted high binding affinity peptides of human papillomavirus type 18 proteins E6 and E7. Clin Cancer Res 2001; 7:788s–795s.Google ScholarPubMed
Sandborn, WJ, Feagan, BG, Hanauer, SB, Present, DH, Sutherland, LR, Kamm, MA, Wolf, DC, Baker, JP, Hawkey, C, Archambault, A, et al. An engineered human antibody to TNF (CDP571) for active Crohn's disease: a randomized double-blind placebo-controlled trial. Gastroenterology 2001; 120:1330–1338.CrossRefGoogle ScholarPubMed
Sandborn, WJ, Feagan, BG, Stoinov, S, Honiball, PJ, Rutgeerts, P, Mason, D, Bloomfield, R, Schreiber, S, and PRECISE 1 Study Investigators. Certolizumab pegol for the treatment of Crohn's disease. N Engl J Med 2007; 357:228–238.CrossRefGoogle ScholarPubMed
Sauter, A, Kloft, C, Gronau, S, Bogeschdorfer, F, Erhardt, T, Golze, W, Schroen, C, Staab, A, Riechelmann, H, and Hoermann, K. Pharmacokinetics, immunogenicity and safety of bivatuzumab mertansine, a novel CD44v6-targeting immunoconjugate, in patients with squamous cell carcinoma of the head and neck. Int J Oncol 2007; 30:927–935.Google ScholarPubMed
Sawada, T, Nishihara, T, Yamamoto, A, Teraoka, H, Yamashita, Y, Okamura, T, Ochi, H, Ho, JJ, Kim, YS, and Hirakawa, K. Preoperative clinical radioimmunodetection of pancreatic cancer by 111 In-labeled chimeric monoclonal antibody Nd2. Jpn J Cancer Res 1999; 90:1179–1186.CrossRefGoogle ScholarPubMed
Schreiber, S, Rutgeerts, P, Fedorak, RN, Khaliq-Kareemi, M, Kamm, MA, Boivin, M, Bernstein, CN, Staun, M, Thomsen, OØ, Innes, A, et al. A randomized, placebo-controlled trial of certolizumab pegol (CDP870) for treatment of Crohn's disease. Gastroenterology 2005; 129:807–818.CrossRefGoogle ScholarPubMed
Schreiber, S, Khaliq-Kareemi, M, Lawrance, IC, OØ, Thomsen, Hanauer, SB, McColm, J, Bloomfield, R, Sandborn, WJ, and PRECISE 2 Study Investigators. Maintenance therapy with certolizumab pegol for Crohn's disease. N Engl J Med 2007; 357:239–250.CrossRefGoogle ScholarPubMed
Schroeder, TJ, First, MR, Hurtubise, PE, Marmer, DJ, Martin, DM, Mansour, ME, and Melvin, DB. Immunologic monitoring with Orthoclone OKT3 therapy. J Heart Transplant 1989; 8:371–380.Google ScholarPubMed
Scott, AM, Lee, FT, Jones, R, Hopkins, W, MacGregor, D, Cebon, JS, Hannah, A, Chong, G, U, P, Papenfuss, A, et al. A phase I trial of humanized monoclonal antibody A33 in patients with colorectal carcinoma: biodistribution, pharmacokinetics, and quantitative tumor uptake. Clin Cancer Res 2005; 11:4810–4817.CrossRefGoogle ScholarPubMed
Segal, MR, Cummings, MP, and Hubbard, AE. Relating amino acid sequence to phenotype: analysis of peptide-binding data. Biometrics 2001; 57:632–642.CrossRefGoogle ScholarPubMed
Sette, A, Buus, S, Appella, E, Smith, JA, Chesnut, R, Miles, C, Colon, SM, and Grey, HM. Prediction of major histocompatibility complex binding regions of protein antigens by sequence pattern analysis. Proc Natl Acad Sci USA 1989; 86:3296–3300.CrossRefGoogle ScholarPubMed
Sidney, J, Southwood, S, Oseroff, C, del Guerico, MF, Grey, HM, and Sette, A. Measurement of MHC/peptide interactions by gel filtration. In: Current Protocols in Immunology, Wiley, New York (1998):18.13.1–18.13.19.Google Scholar
Singh, H and , Raghava GP. ProPred: prediction of HLA-DR binding sites. Bioinformatics 2001; 17:1236–1237.CrossRefGoogle ScholarPubMed
Southwood, S, Sidney, J, Kondo, A, del Guercio, MF, Appella, E, Hoffman, S, Kubo, RT, Chesnut, RW, Grey, HM, and Sette, A. Several common HLA-DR types share largely overlapping peptide binding repertoires. J Immunol 1998; 160:3363–3373.Google ScholarPubMed
Starr, TK, Jameson, SC, and Hogquist, KA. Positive and negative selection of T cells. Annu Rev Immunol 2003; 21:139–176.CrossRefGoogle ScholarPubMed
Steinfeld, SD, Tant, L, Burmester, GR, Teoh, NK, Wegener, WA, Goldenberg, DM, and Pradier, O. Epratuzumab (humanised anti-CD22 antibody) in primary Sjögren's syndrome: an open-label phase I/II study. Arthritis Res Ther 2006; 8:R129.CrossRefGoogle ScholarPubMed
Stickler, M, Chin, R, Faravashi, N, Gebel, W, Razo, OJ, Rochanayon, N, Power, S, Valdes, AM, Holmes, S, and Harding, FA. Human population-based identification of CD4+ T-cell peptide epitope determinants. J Immunol Methods 2003; 281:95–108.CrossRefGoogle ScholarPubMed
Stickler, M, Rochanayon, N, Razo, OJ, Mucha, J, Gebel, W, Faravashi, N, Chin, R, Holmes, S, and Harding, FA. An in vitro human cell-based assay to rank the relative immunogenicity of proteins. Toxicol Sci 2004; 77:280–289.CrossRefGoogle Scholar
Stroomer, JW, Roos, JC, Sproll, M, Quak, JJ, Heider, KH, Wilhelm, BJ, Castelijns, JA, Meyer, R, Kwakkelstein, MO, Snow, GB, et al. Safety and biodistribution of 99mTechnetium-labeled anti-CD44v6 monoclonal antibody BIWA 1 in head and neck cancer patients. Clin Cancer Res 2000; 6:3046–3055.Google ScholarPubMed
Sturniolo, T, Bono, E, Ding, J, Raddrizzani, L, Tuereci, O, Sahin, U, Braxenthaler, M, Gallazzi, F, Protti, MP, Sinigaglia, F, et al. Generation of tissue-specific and promiscuous HLA ligand databases using DNA microarrays and virtual HLA class II matrices. Nat Biotechnol 1999; 17:555–561.CrossRefGoogle ScholarPubMed
Tangri, S, Mothé, BR, Eisenbraun, J, Sidney, J, Southwood, S, Briggs, K, Zinckgraf, J, Bilsel, P, Newman, M, Chesnut, R, et al. Rationally engineered therapeutic proteins with reduced immunogenicity. J Immunol 2005; 174:3187–3196.CrossRefGoogle ScholarPubMed
Targan, SR, Hanauer, SB, Deventer, SJ, Mayer, L, Present, DH, Braakman, T, DeWoody, KL, Schaible, TF, and Rutgeerts, PJ. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group. N Engl J Med 1997; 337: 1029–1035.CrossRefGoogle ScholarPubMed
Tcheng, JE, Kereiakes, DJ, Lincoff, AM, George, BS, Kleiman, NS, Sane, DC, Cines, DB, Jordan, RE, Mascelli, MA, Langrall, MA, et al. Abciximab readministration: results of the ReoPro Readministration Registry. Circulation 2001; 104:870–875.CrossRefGoogle ScholarPubMed
,The Impact-RSV Study Group. Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. Pediatrics 2006; 102:531–537.Google Scholar
Tijink, BM, Buter, J, Bree, R, Giaccone, G, Lang, MS, Staab, A, Leemans, CR, Dongen, GA. A phase I dose escalation study with anti-CD44v6 bivatuzumab mertansine in patients with incurable squamous cell carcinoma of the head and neck or esophagus. Clin Cancer Res 2006; 12:6064–6072.CrossRefGoogle ScholarPubMed
Tolcher, AW, Ochoa, L, Hammond, , Patnaik, A, Edwards, T, Takimoto, C, Smith, L, Bono, J, Schwartz, G, Mays, T, et al. Cantuzumab mertansine, a maytansinoid immunoconjugate directed to the CanAg antigen: a phase I, pharmacokinetic, and biologic correlative study. J Clin Oncol 2003; 21:211–222.CrossRefGoogle ScholarPubMed
Uckun, FM, Messinger, Y, Chen, CL, O'Neill, K, Myers, , Goldman, F, Hurvitz, C, Casper, JT, and Levine, A. Treatment of therapy-refractory B-lineage acute lymphoblastic leukemia with an apoptosis-inducing CD19-directed tyrosine kinase inhibitor. Clin Cancer Res 1999; 5:3906–3913.Google ScholarPubMed
Walle, I, Gansemans, Y, Parren, PW, Stas, P, and Lasters, I. Immunogenicity screening in protein drug development. Expert Opin Biol Ther 2007; 7:405–418.CrossRefGoogle ScholarPubMed
Putte, LB, Atkins, C, Malaise, M, Sany, J, Russell, AS, Riel, PL, Settas, L, Bijlsma, JW, Todesco, S, Dougados, M, et al. Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed. Ann Rheum Dis 2004; 63:508–516.CrossRefGoogle ScholarPubMed
Zanten-Przybysz, I, Molthoff, C, Gebbinck, JK, Mensdorff-Pouilly, S, Verstraeten, R, Kenemans, P, and Verheijen, R. Cellular and humoral responses after multiple injections of unconjugated chimeric monoclonal antibody MOv18 in ovarian cancer patients: a pilot study. J Cancer Res Clin Oncol 2002; 128:484–492.CrossRefGoogle ScholarPubMed
Vermeire, S, Noman, M, Assche, G, Baert, F, D'Haens, G, and Rutgeerts, P. Effectiveness of concomitant immunosuppressive therapy in suppressing the formation of antibodies to infliximab in Crohn's disease. Gut 2007; 56:1226–1231.CrossRefGoogle ScholarPubMed
Vincenti, F, Lantz, M, Birnbaum, J, Garovoy, M, Mould, D, Hakimi, J, Nieforth, K, and Light, S. Aphase I trial of humanized anti-interleukin 2 receptor antibody in renal transplantation. Transplantation 1997; 63:33–38.CrossRefGoogle ScholarPubMed
Warmerdam, PA, Vanderlick, K, Vandervoort, P, Smedt, H, Plaisance, S, Maeyer, M, and Collen, D. Staphylokinase-specific cell-mediated immunity in humans. J Immunol 2002; 168:155–161.CrossRefGoogle ScholarPubMed
Weinblatt, ME, Maddison, PJ, Bulpitt, KJ, Hazleman, BL, Urowitz, MB, Sturrock, RD, Coblyn, JS, Maier, AL, Spreen, WR, Manna, VK, et al. CAMPATH-1H, a humanized monoclonal antibody, in refractory rheumatoid arthritis. An intravenous dose-escalation study. Arthritis Rheum 1995; 38:1589–1594.CrossRefGoogle ScholarPubMed
Weinblatt, ME, Keystone, EC, Furst, , Moreland, LW, Weisman, MH, Birbara, CA, Teoh, , Fischkoff, SA, and , Chartash EK. Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum 2003; 48:35–45.CrossRefGoogle ScholarPubMed
Welt, S, Ritter, G, Williams, C, Cohen, LS, John, M, Jungbluth, A, Richards, EA, Old, LJ, and Kemeny, NE. Phase I study of anticolon cancer humanized antibody A33. Clin Cancer Res 2003a; 9:1338–1346.Google ScholarPubMed
Welt, S, Ritter, G, Williams, C, Cohen, LS, Jungbluth, A, Richards, EA, Old, LJ, and Kemeny, NE. Preliminary report of a phase I study of combination chemotherapy and humanized A33 antibody immunotherapy in patients with advanced colorectal cancer. Clin Cancer Res 2003b; 9:1347–1353.Google ScholarPubMed
Zhao, Y, Pinilla, C, Valmori, D, Martin, R, and Simon, R. Application of support vector machines for T-cell epitopes prediction. Bioinformatics 2003; 19:1978–1984.CrossRefGoogle ScholarPubMed
Zhou, LJ and Tedder, TF. CD14+ blood monocytes can differentiate into functionally mature CD83+ dendritic cells. Proc Natl Acad Sci USA 1996; 93:2588–2592.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×