One target, different effects: a comparison of distinct therapeutic antibodies against the same targets

다국어 초록 (Multilingual Abstract)

To date, more than 30 antibodies have been approved worldwide for therapeutic use. While the monoclonal antibody market is rapidly growing, the clinical use of therapeutic antibodies is mostly limited to treatment of cancers and immunological disorders. Moreover, antibodies against only five targets (TNF-α, HER2, CD20,EGFR, and VEGF) account for more than 80 percent of the worldwide market of therapeutic antibodies. The shortage of novel, clinically proven targets has resulted in the development of many distinct therapeutic antibodies against a small number of proven targets,based on the premise that different antibody molecules against the same target antigen have distinct biological and clinical effects from one another. For example,four antibodies against TNF-α have been approved by the FDA -- infliximab, adalimumab, golimumab, and certolizumab pegol -- with many more in clinical and preclinical development. The situation is similar for HER2, CD20, EGFR, and VEGF, each having one or more approved antibodies and many more under development. This review discusses the different binding characteristics, mechanisms of action, and biological and clinical activities of multiple monoclonal antibodies against TNF-α, HER-2, CD20, and EGFR and provides insights into the development of therapeutic antibodies.

참고문헌 (Reference)

1 Persson M, "[(177)Lu]pertuzumab: experimental studies on targeting of HER-2 positive tumour cells" 32 : 1457-1462, 2005

2 Palframan R, "Use of biofluorescence imaging to compare the distribution of certolizumab pegol, adalimumab, and infliximab in the inflamed paws of mice with collagen-induced arthritis" 348 : 36-41, 2009

3 Izumi Y, "Tumour biology: Herceptin acts as an anti-angiogenic cocktail" 416 : 279-280, 2002

4 Alonso-Ruiz A, "Tumor necrosis factor alpha drugs in rheumatoid arthritis: systematic review and metaanalysis of efficacy and safety" 9 : 52-, 2008

5 Valabrega G, "Trastuzumab: mechanism of action, resistance and future perspectives in HER2-overexpressing breast cancer" 18 : 977-984, 2007

6 Arnould L, "Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism" 94 : 259-267, 2006

7 Ghosh R, "Trastuzumab has preferential activity against breast cancers driven by HER2 homodimers" 71 : 1871-1882, 2011

8 Barok M, "Trastuzumab causes antibody-dependent cellular cytotoxicity-mediated growth inhibition of submacroscopic JIMT-1 breast cancer xenografts despite intrinsic drug resistance" 6 : 2065-2072, 2007

9 Hudis CA, "Trastuzumab - mechanism of action and use in clinical practice" 357 : 39-51, 2007

10 Molina MA, "Trastuzumab (herceptin), a humanized anti-Her2 receptor monoclonal antibody, inhibits basal and activated Her2 ectodomain cleavage in breast cancer cells" 61 : 4744-4749, 2001

11 Maini RN, "Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis" 41 : 1552-1563, 1998

12 Kristensen LE, "The number needed to treat for adalimumab, etanercept, and infliximab based on ACR50 response in three randomized controlled trials on established rheumatoid arthritis: a systematic literature review" 36 : 411-417, 2007

13 Byrd JC, "The mechanism of tumor cell clearance by rituximab in vivo in patients with B-cell chronic lymphocytic leukemia: evidence of caspase activation and apoptosis induction" 99 : 1038-1043, 2002

14 Pedersen IM, "The chimeric anti-CD20 antibody rituximab induces apoptosis in B-cell chronic lymphocytic leukemia cells through a p38 mitogen activated protein-kinase-dependent mechanism" 99 : 1314-1319, 2002

15 Teeling JL, "The biological activity of human CD20 monoclonal antibodies is linked to unique epitopes on CD20" 177 : 362-371, 2006

16 Nahta R, "The HER-2-targeting antibodies trastuzumab and pertuzumab synergistically inhibit the survival of breast cancer cells" 64 : 2343-2346, 2004

17 Baselga J, "The EGFR as a target for anticancer therapy - focus on cetuximab" 37 : S16-S22, 2001

18 Agus DB, "Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor growth" 2 : 127-137, 2002

19 Kim GP, "Targeting colorectal cancer with human anti-EGFR monoclonocal antibodies: focus on panitumumab" 2 : 223-228, 2008

20 Mahtani RL, "Synergy between cetuximab and chemotherapy in tumors of the gastrointestinal tract" 13 : 39-50, 2008

21 Li S, "Structural basis for inhibition of the epidermal growth factor receptor by cetuximab" 7 : 301-311, 2005

22 Feldmann M, "Role of cytokines in rheumatoid arthritis" 14 : 397-440, 1996

23 Skvortsova I, "Rituximab enhances radiation-triggered apoptosis in non-Hodgkin’'s lymphoma cells via caspase-dependent and - independent mechanisms" 47 : 183-196, 2006

24 McLaughlin P, "Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: Half of patients respond to a four-dose treatment program" 16 : 2828-2833, 1998

25 Genentech, "Rituxan full prescribing information"

26 Gennari R, "Pilot study of the mechanism of action of preoperative trastuzumab in patients with primary operable breast tumors overexpressing HER2" 10 : 5650-5655, 2004

27 Saltz LB, "Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor" 22 : 1201-1208, 2004

28 Ritchlin C, "Patterns of cytokine production in psoriatic synovium" 25 : 1544-1552, 1998

29 Messersmith WA, "Panitumumab, a monoclonal anti epidermal growth factor receptor antibody in colorectal cancer: another one or the one" 13 : 4664-4666, 2007

30 Cohenuram M, "Panitumumab the first fully human monoclonal antibody: from the bench to the clinic" 18 : 7-15, 2007

31 Freeman D, "Panitumumab and cetuximab epitope mapping and in vitro activity" 26 (26): 14536-, 2008

32 Nagata Y, "PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients" 6 : 117-127, 2004

33 Kaneko E, "Optimizing therapeutic antibody function: progress with Fc domain engineering" 25 : 1-11, 2011

34 Craigen JL, "Ofatumumab, a human mab targeting a membrane-proximal small-loop epitope on CD20, induces potent NK cell-mediated ADCC" 114 : 1725-, 2009

35 Mandal M, "Nuclear targeting of Bax during apoptosis in human colorectal cancer cells" 17 : 999-1007, 1998

36 Ramakrishnan MS, "Nimotuzumab, a promising therapeutic monoclonal for treatment of tumors of epithelial origin" 1 : 41-48, 2009

37 Petit AM, "Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo: angiogenic implications for signal transduction therapy of solid tumors" 151 : 1523-1530, 1997

38 Cooley S, "Natural killer cell cytotoxicity of breast cancer targets is enhanced by two distinct mechanisms of antibody-dependent cellular cytotoxicity against LFA-3 and HER2/neu" 27 : 1533-1541, 1999

39 Press OW, "Monoclonal antibody 1F5 (anti-CD20) serotherapy of human B cell lymphomas" 69 : 584-591, 1987

40 Huang SM, "Molecular inhibition of angiogenesis and metastatic potential in human squamous cell carcinomas after epidermal growth factor receptor blockade" 1 : 507-514, 2002

41 Einfeld DA, "Molecular cloning of the human B cell CD20 receptor predicts a hydrophobic protein with multiple transmembrane domains" 7 : 711-717, 1988

42 Flieger D, "Mechanism of cytotoxicity induced by chimeric mouse human monoclonal antibody IDEC-C2B8 in CD20-expressing lymphoma cell lines" 204 : 55-63, 2000

43 Nesbitt A, "Mechanism of action of certolizumab pegol (CDP870): in vitro comparison with other anti-tumor necrosis factor alpha agents" 13 : 1323-1332, 2007

44 Junttila TT, "Ligandindependent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941" 15 : 429-440, 2009

45 Lièvre A, "KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer" 66 : 3992-3995, 2006

46 Wu X, "Involvement of p27KIP1 in G1 arrest mediated by an anti-epidermal growth factor receptor monoclonal antibody" 12 : 1397-1403, 1996

47 Schmitz KR, "Interaction of antibodies with ErbB receptor extracellular regions" 315 : 659-670, 2009

48 Franklin MC, "Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex" 5 : 317-328, 2004

49 Clynes RA, "Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets" 6 : 443-446, 2000

50 Rudnick SI, "Influence of affinity and antigen internalization on the uptake and penetration of Anti-HER2 antibodies in solid tumors" 71 : 2250-2259, 2011

51 Musolino A, "Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER-2/neu-positive metastatic breast cancer" 26 : 1789-1796, 2008

52 Emi Aikawa N, "Immunogenicity of anti-TNF-alpha agents in autoimmune diseases" 38 : 82-89, 2010

53 Abbott, "Humira full prescribing information"

54 Schneider-Merck T, "Human IgG2 antibodies against epidermal growth factor receptor effectively trigger antibody-dependent cellular cytotoxicity but, in contrast to IgG1, only by cells of myeloid lineage" 184 : 512-520, 2010

55 Jakobovits A, "From XenoMouse technology to panitumumab, the first fully human antibody product from transgenic mice" 25 : 1134-1143, 2007

56 Hynes NE, "ErbB receptors and signaling pathways in cancer" 21 : 177-184, 2009

57 Yang XD, "Eradication of established tumors by a fully human monoclonal antibody to the epidermal growth factor receptor without concomitant chemotherapy" 59 : 1236-1243, 1999

58 Rockberg J, "Epitope mapping of antibodies using bacterial surface display" 5 : 1039-1045, 2008

59 Vogel CL, "Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer" 20 : 719-726, 2002

60 Lee J, "Effect of Simvastatin on Cetuximab Resistance in Human Colorectal Cancer With KRAS Mutations" OXFORD UNIV PRESS INC 103 (103): 674-688, 2011

61 Nicholson RI, "EGFR and cancer prognosis" 37 (37): S9-S15, 2001

62 Rockberg J, "Discovery of epitopes for targeting the human epidermal growth factor receptor 2 (HER2) with antibodies" 3 : 238-247, 2009

63 Lewis GD, "Differential responses of human tumor cell lines to anti-p185HER2 monoclonal antibodies" 37 : 255-263, 1993

64 Meira DD, "Different antiproliferative effects of matuzumab and cetuximab in A431 cells are associated with persistent activity of the MAPK pathway" 45 : 1265-1273, 2009

65 Uchiyama S, "Development of novel humanized anti-CD20 antibodies based on affinity constant and epitope" 101 : 201-209, 2010

66 Kute T, "Development of herceptin resistance in breast cancer cells" 57 : 86-93, 2004

67 Dunn EF, "Dasatinib sensitizes KRAS mutant colorectal tumors to cetuximab" 30 : 561-574, 2011

68 Williams RO, "Cytokine inhibitors in rheumatoid arthritis and other autoimmune diseases" 7 : 412-417, 2007

69 Soomin Yoon, "Current Perspectives on Therapeutic Antibodies" 한국생물공학회 15 (15): 709-715, 2010

70 Köhler G, "Continuous cultures of fused cells secreting antibody of predefined specificity" 256 : 495-497, 1975

71 Cragg MS, "Complementmediated lysis by anti-CD20 mAb correlates with segregation into lipid rafts" 101 : 1045-1052, 2003

72 Beum PV, "Complement activation on B lymphocytes opsonized with rituximab or ofatumumab produces substantial changes in membrane structure preceding cell lysis" 181 : 822-832, 2008

73 Launois R, "Comparison of certolizumab pegol with other anticytokine agents for treatment of rheumatoid arthritis: A multiple-treatment Bayesian metaanalysis" 38 : 835-845, 2011

74 Kim MS, "Comparative analyses of complex formation and binding sites between human tumor necrosis factor-alpha and its three antagonists elucidate their different neutralizing mechanisms" 374 : 1374-1388, 2007

75 Klos KS, "Combined trastuzumab and paclitaxel treatment better inhibits ErbB-2-mediated angiogenesis in breast carcinoma through a more effective inhibition of Akt than either treatment alone" 98 : 1377-1385, 2003

76 Heinemann V, "Clinical relevance of EGFR- and KRAS-status in colorectal cancer patients treated with monoclonal antibodies directed against the EGFR" 35 : 262-271, 2009

77 "Cimzia full prescribing information"

78 Demidem A, "Chimeric anti-CD20 (IDEC-C2B8) monoclonal antibody sensitizes a B cell lymphoma cell line to cell killing by cytotoxic drugs" 12 : 177-186, 1997

79 Teeling JL, "Characterization of new human CD20 monoclonal antibodies with potent cytolytic activity against non-Hodgkin lymphomas" 104 : 1793-1800, 2004

80 Shealy D, "Characterization of golimumab, a human monoclonal antibody specific for human tumor necrosis factor alpha" 2 : 2010

81 Chung KY, "Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry" 23 : 1803-1810, 2005

82 Cunningham D, "Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer" 351 : 337-345, 2004

83 Kawaguchi Y, "Cetuximab induce antibody-dependent cellular cytotoxicity against EGFR-expressing esophageal squamous cell carcinoma" 120 : 781-787, 2007

84 Gebbia V, "Cetuximab in squamous cell head and neck carcinomas" 18 : 5-7, 2007

85 Cassinotti A, "Certolizumab pegol: an evidence-based review of its place in the treatment of Crohn’s disease" 2 : 209-229, 2008

86 Rivkin A, "Certolizumab pegol for the management of Crohn’'s disease in adults" 31 : 1158-1176, 2009

87 Beers SA, "CD20 as a target for therapeutic type I and II monoclonal antibodies" 47 : 107-114, 2010

88 Müller D, "Bispecific antibodies for cancer immunotherapy: Current perspectives" 24 : 89-98, 2010

89 Goldstein NI, "Biological efficacy of a chimeric antibody to the epidermal growth factor receptor in a human tumor xenograft model" 1 : 1311-1318, 1995

90 Kohno T, "Binding characteristics of tumor necrosis factor receptor-Fc fusion proteins vs anti-tumor necrosis factor mAbs" 12 : 5-8, 2007

91 Genentech, "BLA Supplement: HERCEPTIN"

92 zum Buschenfelde CM, "Antihuman epidermal growth factor receptor 2 (HER2) monoclonal antibody trastuzumab enhances cytolytic activity of class I-restricted HER2-specific T lymphocytes against HER2-overexpressing tumor cells" 62 : 2244-2247, 2002

93 Carter PJ, "Antibody-drug conjugates for cancer therapy" 14 : 154-169, 2008

94 Kurai J, "Antibody-dependent cellular cytotoxicity mediated by cetuximab against lung cancer cell lines" 13 : 1552-1561, 2007

95 Cragg MS, "Antibody specificity controls in vivo effector mechanisms of anti-CD20 reagents" 103 : 2738-2743, 2004

96 Clark M, "Antibody humanization: a case of the ‘Emperor’s new clothes’" 21 : 397-402, 2000

97 Kiyota A, "Anti-epidermal growth factor receptor monoclonal antibody 225 upregulates p27(KIP1) and p15(INK4B) and induces G1 arrest in oral squamous carcinoma cell lines" 63 : 92-98, 2002

98 Perrotte P, "Anti-epidermal growth factor receptor antibody C225 inhibits angiogenesis in human transitional cell carcinoma growing orthotopically in nude mice" 5 : 257-265, 1999

99 Spiridon CI, "A comparison of the in vitro and in vivo activities of IgG and F(ab')2 fragments of a mixture of three monoclonal anti-Her-2 antibodies" 10 : 3542-3551, 2004