Abstract
Infused antibodies are the most successful immune-based agents to treat certain cancers. However, their modes of action are not always dependent on immune mechanisms aside from antigen-specific targeting. Immune mechanisms include direct and indirect cytotoxicity while nonimmune mechanisms include the targeting of toxins, such as drugs or irradiation sources, directly to the tumor, the subject of Chap. 12. Therapeutic antibodies can be chimeric or humanized (part human and part animal, usually mouse), but fully human antibodies are in trials or have been FDA approved. This chapter will summarize the current FDA-approved antibodies to treat cancer, and highlight promising antibodies in development.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Gensini GF, Conti AA, Lippi D (2007) The contributions of Paul Ehrlich to infectious disease. J Infect 54:221–224
Silverstein AM (2002) The collected papers of Paul Ehrlich: why was volume 4 never published? Bull Hist Med 76:335–339
Pastan I, Hassan R, Fitzgerald DJ, Kreitman RJ (2006) Immunotoxin therapy of cancer. Nat Rev\ 6:559–565
Kreitman RJ, Pastan I (2006) Immunotoxins in the treatment of hematologic malignancies. Curr Drug Targets 7:1301–1311
Akhtar S, Maghfoor I (2002) Rituximab plus CHOP for diffuse large-B-cell lymphoma. N Engl J Med 346:1830–1831, author reply 1830–1831
Keating MJ et al (2002) Therapeutic role of alemtuzumab (Campath-1 H) in patients who have failed fludarabine: results of a large international study. Blood 99:3554–3561
Shankaran V et al (2001) IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 410:1107–1111
Scott AM, Wolchok JD, Old LJ (2012) Antibody therapy of cancer. Nat Rev Cancer 12:278–287
Sharma P, Wagner K, Wolchok JD, Allison JP (2012) Novel cancer immunotherapy agents with survival benefit: recent successes and next steps. Nat Rev Cancer 11:805–812
Clynes RA, Towers TL, Presta LG, Ravetch JV (2000) Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets. Nat Med 6:443–446
Dhodapkar KM, Krasovsky J, Williamson B, Dhodapkar MV (2002) Antitumor monoclonal antibodies enhance cross-presentation of cellular antigens and the generation of myeloma-specific killer T cells by dendritic cells. J Exp Med 195:125–133
Weiner LM, Surana R, Wang S (2010) Monoclonal antibodies: versatile platforms for cancer immunotherapy. Nat Rev Immunol 10:317–327
Nimmerjahn F, Ravetch JV (2010) Antibody-mediated modulation of immune responses. Immunol Rev 236:265–275
Nimmerjahn F, Ravetch JV (2008) Fcgamma receptors as regulators of immune responses. Nat Rev Immunol 8:34–47
Nimmerjahn F, Ravetch JV (2007) Fc-receptors as regulators of immunity. Adv Immunol 96:179–204
Nimmerjahn F, Ravetch JV (2007) Antibodies, Fc receptors and cancer. Curr Opin Immunol 19:239–245
Gualberto A (2012) Brentuximab Vedotin (SGN-35), an antibody-drug conjugate for the treatment of CD30-positive malignancies. Expert Opin Investig Drugs 21:205–216
Hooks MA, Wade CS, Millikan WJ Jr (1991) Muromonab CD-3: a review of its pharmacology, pharmacokinetics, and clinical use in transplantation. Pharmacotherapy 11:26–37
Kohler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495–497
Castillo FJ et al (1994) Hybridoma stability. Dev Biol Stand 83:55–64
Castillo FJ, Mullen LJ, Thrift JC, Grant BC (1992) Perfusion cultures of hybridoma cells for monoclonal antibody production. Ann N Y Acad Sci 665:72–80
Ma JK et al (1998) Characterization of a recombinant plant monoclonal secretory antibody and preventive immunotherapy in humans. Nat Med 4:601–606
Green LL (1999) Antibody engineering via genetic engineering of the mouse: XenoMouse strains are a vehicle for the facile generation of therapeutic human monoclonal antibodies. J Immunol Methods 231:11–23
Hoogenboom HR, Chames P (2000) Natural and designer binding sites made by phage display technology. Immunol Today 21:371–378
Vaughan TJ, Osbourn JK, Tempest PR (1998) Human antibodies by design. Nat Biotechnol 16:535–539
Adair JR (1992) Engineering antibodies for therapy. Immunol Rev 130:5–40
Morrison SL, Oi VT (1989) Genetically engineered antibody molecules. Adv Immunol 44:65–92
Krauss J (2003) Recombinant antibodies for the diagnosis and treatment of cancer. Mol Biotechnol 25:1–17
Peterson NC (1996) Recombinant antibodies: alternative strategies for developing and manipulating murine-derived monoclonal antibodies. Lab Anim Sci 46:8–14
Hohmann A, Cairns E, Brisco M, Bell DA, Diamond B (1995) Immunoglobulin gene sequence analysis of anti-cardiolipin and anti-cardiolipin idiotype (H3) human monoclonal antibodies. Autoimmunity 22:49–58
Zangemeister-Wittke U (2005) Antibodies for targeted cancer therapy—technical aspects and clinical perspectives. Pathobiology 72:279–286
Kipriyanov SM, Le Gall F (2004) Generation and production of engineered antibodies. Mol Biotechnol 26:39–60
Berger M, Shankar V, Vafai A (2002) Therapeutic applications of monoclonal antibodies. Am J Med Sci 324:14–30
Lonial S et al (2012) Elotuzumab in combination with lenalidomide and low-dose dexamethasone in relapsed or refractory multiple myeloma. J Clin Oncol 30(16):1953–9
Richardson PG, Lonial S, Jakubowiak AJ, Harousseau JL, Anderson KC (2011) Monoclonal antibodies in the treatment of multiple myeloma. Br J Haematol 10.1111/j.1365-2141.2011.08790.x
Reff ME et al (1994) Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood 83:435–445
Flieger D, Renoth S, Beier I, Sauerbruch T, Schmidt-Wolf I (2000) Mechanism of cytotoxicity induced by chimeric mouse human monoclonal antibody IDEC-C2B8 in CD20-expressing lymphoma cell lines. Cell Immunol 204:55–63
Di Gaetano N et al (2003) Complement activation determines the therapeutic activity of rituximab in vivo. J Immunol 171:1581–1587
Uchida J et al (2004) The innate mononuclear phagocyte network depletes B lymphocytes through Fc receptor-dependent mechanisms during anti-CD20 antibody immunotherapy. J Exp Med 199:1659–1669
Racila E et al (2008) A polymorphism in the complement component C1qA correlates with prolonged response following rituximab therapy of follicular lymphoma. Clin Cancer Res 14:6697–6703
Cragg MS, Glennie MJ (2004) Antibody specificity controls in vivo effector mechanisms of anti-CD20 reagents. Blood 103:2738–2743
Kennedy AD et al (2004) Rituximab infusion promotes rapid complement depletion and acute CD20 loss in chronic lymphocytic leukemia. J Immunol 172:3280–3288
Cartron G et al (2002) Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene. Blood 99:754–758
Weng WK, Levy R (2003) Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma. J Clin Oncol 21:3940–3947
Cartron G, Watier H, Golay J, Solal-Celigny P (2004) From the bench to the bedside: ways to improve rituximab efficacy. Blood 104:2635–2642
Gordon AN et al (2004) CA125- and tumor-specific T-cell responses correlate with prolonged survival in oregovomab-treated recurrent ovarian cancer patients. Gynecol Oncol 94:340–351
Hilchey SP et al (2009) Rituximab immunotherapy results in the induction of a lymphoma idiotype-specific T-cell response in patients with follicular lymphoma: support for a “vaccinal effect” of rituximab. Blood 113:3809–3812
Byrd JC et al (2002) 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. Blood 99:1038–1043
Coiffier B et al (2002) CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 346:235–242
Forstpointner R et al (2004) The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood 104:3064–3071
Reid E, Nooka A, Blackmon J, Lechowicz MJ (2012) Clinical use of rituximab in patients with HIV related lymphoma and Multicentric Castleman’s disease. Curr Drug Deliv 9:41–51
Beers SA et al (2010) Antigenic modulation limits the efficacy of anti-CD20 antibodies: implications for antibody selection. Blood 115:5191–5201
Khan KD et al (2006) A phase 2 study of rituximab in combination with recombinant interleukin-2 for rituximab-refractory indolent non-Hodgkin’s lymphoma. Clin Cancer Res 12:7046–7053
Bodogai M et al (2012) Failure of Rituximab in solid tumors is due to its inability to eliminate tumor evoked B regulatory cells. J Immunol 165:115
Cheson BD (2010) Ofatumumab, a novel anti-CD20 monoclonal antibody for the treatment of B-cell malignancies. J Clin Oncol 28:3525–3530
Hagenbeek A et al (2008) First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase 1/2 trial. Blood 111:5486–5495
Coiffier B et al (2008) Safety and efficacy of ofatumumab, a fully human monoclonal anti-CD20 antibody, in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: a phase 1–2 study. Blood 111:1094–1100
Teeling JL et al (2006) The biological activity of human CD20 monoclonal antibodies is linked to unique epitopes on CD20. J Immunol 177:362–371
Teeling JL et al (2004) Characterization of new human CD20 monoclonal antibodies with potent cytolytic activity against non-Hodgkin lymphomas. Blood 104:1793–1800
Kahl BS, Cheson BD, Friedberg JW (2010) Clinical Roundtable Monograph: current treatment options for NHL patients refractory to standard therapy: recent data in single-agent and combination therapy. Clin Adv Hematol Oncol 8:1–16
De Mattos-Arruda L, Cortes J (2012) Advances in first-line treatment for patients with HER-2+ metastatic breast cancer. Oncologist 17(5):631–44
Hsieh AC, Moasser MM (2007) Targeting HER proteins in cancer therapy and the role of the non-target HER3. Br J Cancer 97:453–457
Moasser MM (2007) Targeting the function of the HER2 oncogene in human cancer therapeutics. Oncogene 26:6577–6592
Sliwkowski MX (2003) Ready to partner. Nat Struct Biol 10:158–159
Sierke SL, Cheng K, Kim HH, Koland JG (1997) Biochemical characterization of the protein tyrosine kinase homology domain of the ErbB3 (HER3) receptor protein. Biochem J 322(Pt 3):757–763
Tzahar E et al (1996) A hierarchical network of interreceptor interactions determines signal transduction by Neu differentiation factor/neuregulin and epidermal growth factor. Mol Cell Biol 16:5276–5287
Amar S, Roy V, Perez EA (2009) Treatment of metastatic breast cancer: looking towards the future. Breast Cancer Res Treat 114:413–422
Perez EA et al (2011) Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31. J Clin Oncol 29:3366–3373
Seidman A et al (2002) Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol 20:1215–1221
Nahta R, Yu D, Hung MC, Hortobagyi GN, Esteva FJ (2006) Mechanisms of disease: understanding resistance to HER2-targeted therapy in human breast cancer. Nat Clin Pract Oncol 3:269–280
Perez EA, Spano JP (2011) Current and emerging targeted therapies for metastatic breast cancer. Cancer 118(12):3014–25
Baselga J et al (2010) Phase II trial of pertuzumab and trastuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer that progressed during prior trastuzumab therapy. J Clin Oncol 28:1138–1144
De Vita F et al (2012) Current status of targeted therapies in advanced gastric cancer. Expert Opin Ther Targets 16(Suppl 2):S29–S34
Okines AF, Cunningham D (2010) Trastuzumab in gastric cancer. Eur J Cancer 46:1949–1959
Hofmann M et al (2008) Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology 52:797–805
Riechmann L, Clark M, Waldmann H, Winter G (1988) Reshaping human antibodies for therapy. Nature 332:323–327
Demko S, Summers J, Keegan P, Pazdur R (2008) FDA drug approval summary: alemtuzumab as single-agent treatment for B-cell chronic lymphocytic leukemia. Oncologist 13:167–174
Hillmen P et al (2007) Alemtuzumab compared with chlorambucil as first-line therapy for chronic lymphocytic leukemia. J Clin Oncol 25:5616–5623
Kennedy GA et al (2003) Treatment of patients with advanced mycosis fungoides and Sezary syndrome with alemtuzumab. Eur J Haematol 71:250–256
Lundin J et al (2003) Phase 2 study of alemtuzumab (anti-CD52 monoclonal antibody) in patients with advanced mycosis fungoides/Sezary syndrome. Blood 101:4267–4272
de Gramont A et al (2011) From chemotherapy to targeted therapy in adjuvant treatment for stage III colon cancer. Semin Oncol 38:521–532
Klapper LN, Kirschbaum MH, Sela M, Yarden Y (2000) Biochemical and clinical implications of the ErbB/HER signaling network of growth factor receptors. Adv Cancer Res 77:25–79
Olayioye MA, Neve RM, Lane HA, Hynes NE (2000) The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J 19:3159–3167
Cohen S, Carpenter G, King L Jr (1980) Epidermal growth factor-receptor-protein kinase interactions. Co-purification of receptor and epidermal growth factor-enhanced phosphorylation activity. J Biol Chem 255:4834–4842
Mendelsohn J, Baselga J (2000) The EGF receptor family as targets for cancer therapy. Oncogene 19:6550–6565
Sato JD et al (1983) Biological effects in vitro of monoclonal antibodies to human epidermal growth factor receptors. Mol Biol Med 1:511–529
Goldstein NI, Prewett M, Zuklys K, Rockwell P, Mendelsohn J (1995) Biological efficacy of a chimeric antibody to the epidermal growth factor receptor in a human tumor xenograft model. Clin Cancer Res 1:1311–1318
Wheeler DL et al (2008) Mechanisms of acquired resistance to cetuximab: role of HER (ErbB) family members. Oncogene 27:3944–3956
Van Cutsem E et al (2009) Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 360:1408–1417
Bokemeyer C et al (2009) Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol 27:663–671
Andreyev HJ, Norman AR, Cunningham D, Oates JR, Clarke PA (1998) Kirsten ras mutations in patients with colorectal cancer: the multicenter “RASCAL” study. J Natl Cancer Inst 90:675–684
Benvenuti S et al (2007) Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. Cancer Res 67:2643–2648
Tol J, Nagtegaal ID, Punt CJ (2009) BRAF mutation in metastatic colorectal cancer. N Engl J Med 361:98–99
Alberts SR et al (2012) Effect of oxaliplatin, fluorouracil, and leucovorin with or without cetuximab on survival among patients with resected stage III colon cancer: a randomized trial. JAMA 307:1383–1393
Weickhardt AJ et al (2012) Dual targeting of the epidermal growth factor receptor using the combination of cetuximab and erlotinib: preclinical evaluation and results of the phase II DUX study in chemotherapy-refractory, advanced colorectal cancer. J Clin Oncol 30:1505–1512
Bonner JA et al (2009) Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol 11:21–28
Burtness B et al (2005) Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an Eastern Cooperative Oncology Group study. J Clin Oncol 23:8646–8654
Rivera F, Garcia-Castano A, Vega N, Vega-Villegas ME, Gutierrez-Sanz L (2009) Cetuximab in metastatic or recurrent head and neck cancer: the EXTREME trial. Expert Rev Anticancer Ther 9:1421–1428
Kabolizadeh P, Kubicek GJ, Heron DE, Ferris RL, Gibson MK (2012) The role of cetuximab in the management of head and neck cancers. Expert Opin Biol Ther 12:517–528
Petrelli F, Borgonovo K, Cabiddu M, Ghilardi M, Barni S (2011) Risk of anti-EGFR monoclonal antibody-related hypomagnesemia: systematic review and pooled analysis of randomized studies. Expert Opin Drug Saf 11(Suppl 1):S9–S19
Vermorken JB et al (2007) Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy. J Clin Oncol 25:2171–2177
Perez-Soler R (2003) Can rash associated with HER1/EGFR inhibition be used as a marker of treatment outcome? Oncology 17:23–28
Yang BB et al (2010) Pharmacokinetic and pharmacodynamic perspectives on the clinical drug development of panitumumab. Clin Pharmacokinet 49:729–740
Jonker DJ et al (2007) Cetuximab for the treatment of colorectal cancer. N Engl J Med 357:2040–2048
Van Cutsem E et al (2007) Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 25:1658–1664
Douillard JY et al (2010) Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol 28:4697–4705
Paez JG et al (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304:1497–1500
Lynch TJ et al (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350:2129–2139
Pao W et al (2004) EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci USA 101:13306–13311
Allegra CJ et al (2009) American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy. J Clin Oncol 27:2091–2096
Shigematsu H et al (2005) Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst 97:339–346
Le Calvez F et al (2005) TP53 and KRAS mutation load and types in lung cancers in relation to tobacco smoke: distinct patterns in never, former, and current smokers. Cancer Res 65:5076–5083
Sartore-Bianchi A et al (2009) PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal antibodies. Cancer Res 69:1851–1857
Khambata-Ford S et al (2007) Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J Clin Oncol 25:3230–3237
Kurai J et al (2007) Antibody-dependent cellular cytotoxicity mediated by cetuximab against lung cancer cell lines. Clin Cancer Res 13:1552–1561
Ciardiello F et al (2004) Antitumor activity of ZD6474, a vascular endothelial growth factor receptor tyrosine kinase inhibitor, in human cancer cells with acquired resistance to antiepidermal growth factor receptor therapy. Clin Cancer Res 10:784–793
Bianco R et al (2008) Vascular endothelial growth factor receptor-1 contributes to resistance to anti-epidermal growth factor receptor drugs in human cancer cells. Clin Cancer Res 14:5069–5080
Sok JC et al (2006) Mutant epidermal growth factor receptor (EGFRvIII) contributes to head and neck cancer growth and resistance to EGFR targeting. Clin Cancer Res 12:5064–5073
Morgillo F, Bareschino MA, Bianco R, Tortora G, Ciardiello F (2007) Primary and acquired resistance to anti-EGFR targeted drugs in cancer therapy. Differentiation 75:788–799
Wheeler DL et al (2009) Epidermal growth factor receptor cooperates with Src family kinases in acquired resistance to cetuximab. Cancer Biol Ther 8:696–703
Baselga J, Arteaga CL (2005) Critical update and emerging trends in epidermal growth factor receptor targeting in cancer. J Clin Oncol 23:2445–2459
Siena S, Sartore-Bianchi A, Di Nicolantonio F, Balfour J, Bardelli A (2009) Biomarkers predicting clinical outcome of epidermal growth factor receptor-targeted therapy in metastatic colorectal cancer. J Natl Cancer Inst 101:1308–1324
Hicklin DJ, Ellis LM (2005) Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 23:1011–1027
Kowanetz M, Ferrara N (2006) Vascular endothelial growth factor signaling pathways: therapeutic perspective. Clin Cancer Res 12:5018–5022
Goel S et al (2011) Normalization of the vasculature for treatment of cancer and other diseases. Physiol Rev 91:1071–1121
Hurwitz H et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342
Hochster HS et al (2008) Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: results of the TREE Study. J Clin Oncol 26:3523–3529
Saltz LB et al (2008) Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 26:2013–2019
Giantonio BJ et al (2007) Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 25:1539–1544
Goldberg RM et al (2004) A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 22:23–30
Grothey A et al (2008) Response-independent survival benefit in metastatic colorectal cancer: a comparative analysis of N9741 and AVF2107. J Clin Oncol 26:183–189
Edeline J et al (2012) Comparison of tumor response by Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST in patients treated with sorafenib for hepatocellular carcinoma. Cancer 118:147–156
Krajewski KM et al (2011) Comparison of four early posttherapy imaging changes (EPTIC; RECIST 1.0, tumor shrinkage, computed tomography tumor density, Choi criteria) in assessing outcome to vascular endothelial growth factor-targeted therapy in patients with advanced renal cell carcinoma. Eur Urol 59:856–862
Jiang T, Kambadakone A, Kulkarni NM, Zhu AX, Sahani DV (2012) Monitoring response to antiangiogenic treatment and predicting outcomes in advanced hepatocellular carcinoma using image biomarkers, CT perfusion, tumor density, and tumor size (RECIST). Invest Radiol 47:11–17
Sandler A et al (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355:2542–2550
Reck M et al (2010) Overall survival with cisplatin-gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: results from a randomised phase III trial (AVAiL). Ann Oncol 21:1804–1809
Besse B et al (2010) Bevacizumab safety in patients with central nervous system metastases. Clin Cancer Res 16:269–278
Ramalingam SS et al (2008) Outcomes for elderly, advanced-stage non small-cell lung cancer patients treated with bevacizumab in combination with carboplatin and paclitaxel: analysis of Eastern Cooperative Oncology Group Trial 4599. J Clin Oncol 26:60–65
Miller K et al (2007) Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 357:2666–2676
Miles DW et al (2010) Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol 28:3239–3247
Brufsky AM et al (2011) RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol 29:4286–4293
Robert NJ et al (2011) RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol 29:1252–1260
Cortes J et al (2012) Adverse events risk associated with bevacizumab addition to breast cancer chemotherapy: a meta-analysis. Ann Oncol 23:1130–1137
Jayson GC, Hicklin DJ, Ellis LM (2012) Antiangiogenic therapy-evolving view based on clinical trial results. Nat Rev Clin Oncol 9:297–303
Burkhardt JK et al (2012) Intra-arterial delivery of bevacizumab after blood–brain barrier disruption for the treatment of recurrent glioblastoma: progression-free survival and overall survival. World Neurosurg 77:130–134
Friedman HS et al (2009) Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 27:4733–4740
De Fazio S, Russo E, Ammendola M, Donato Di Paola E, De Sarro G (2012) Efficacy and safety of bevacizumab in glioblastomas. Curr Med Chem 19:972–981
Escudier B et al (2007) Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 370:2103–2111
Rini BI et al (2008) Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol 26:5422–5428
Miljkovic MD, Girotra M, Abraham RR, Erlich RB (2012) Novel medical therapies of recurrent and metastatic gastroenteropancreatic neuroendocrine tumors. Dig Dis Sci 57:9–18
Burger RA et al (2011) Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 365:2473–2483
Fogelman D et al (2011) Bevacizumab plus gemcitabine and oxaliplatin as first-line therapy for metastatic or locally advanced pancreatic cancer: a phase II trial. Cancer Chemother Pharmacol 68:1431–1438
Casanovas O, Hicklin DJ, Bergers G, Hanahan D (2005) Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell 8:299–309
Batchelor TT et al (2007) AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell 11:83–95
Yan M, Plowman GD (2007) Delta-like 4/Notch signaling and its therapeutic implications. Clinical Cancer Res 13:7243–7246
Fischer C et al (2007) Anti-PlGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels. Cell 131:463–475
D'Amore PA (2007) Vascular endothelial cell growth factor-a: not just for endothelial cells anymore. Am J Pathol 171:14–18
Reinmuth N et al (2001) Induction of VEGF in perivascular cells defines a potential paracrine mechanism for endothelial cell survival. FASEB J 15:1239–1241
Shaheen RM et al (2001) Tyrosine kinase inhibition of multiple angiogenic growth factor receptors improves survival in mice bearing colon cancer liver metastases by inhibition of endothelial cell survival mechanisms. Cancer Res 61:1464–1468
Pietras K, Pahler J, Bergers G, Hanahan D (2008) Functions of paracrine PDGF signaling in the proangiogenic tumor stroma revealed by pharmacological targeting. PLoS Med 5:e19
Moreno Garcia V, Basu B, Molife LR, Kaye SB (2012) Combining antiangiogenics to overcome resistance: rationale and clinical experience. Clin Cancer Res 18(14):3750–61
Neumann F, Zohren F, Haas R (2009) The role of natalizumab in hematopoietic stem cell mobilization. Expert Opin Biol Ther 9:1099–1106
Podar K et al (2011) The selective adhesion molecule inhibitor Natalizumab decreases multiple myeloma cell growth in the bone marrow microenvironment: therapeutic implications. Br J Haematol 155:438–448
Lewiecki EM, Bilezikian JP (2011) Denosumab for the treatment of osteoporosis and cancer-related conditions. Clin Pharmacol Ther 91:123–133
Dore RK (2011) The RANKL pathway and denosumab. Rheum Dis Clin North Am 37:433–452, vi–vii
Baselga J et al (2012) Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 366:109–119
Curiel TJ et al (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10:942–949
Ishida T, Ueda R (2006) CCR4 as a novel molecular target for immunotherapy of cancer. Cancer Sci 97:1139–1146
Yamamoto K et al (2010) Phase I study of KW-0761, a defucosylated humanized anti-CCR4 antibody, in relapsed patients with adult T-cell leukemia-lymphoma and peripheral T-cell lymphoma. J Clin Oncol 28:1591–1598
Antoniu SA (2010) Mogamulizumab, a humanized mAb against C-C chemokine receptor 4 for the potential treatment of T-cell lymphomas and asthma. Curr Opin Mol Ther 12:770–779
Ishida T et al (2012) Defucosylated anti-CCR4 monoclonal antibody (KW-0761) for relapsed adult T-cell leukemia-lymphoma: a multicenter phase II study. J Clin Oncol 30:837–842
Zhang J, Patel L, Pienta KJ (2010) CC chemokine ligand 2 (CCL2) promotes prostate cancer tumorigenesis and metastasis. Cytokine Growth Factor Rev 21:41–48
Rozel S et al (2009) Synergy between anti-CCL2 and docetaxel as determined by DW-MRI in a metastatic bone cancer model. J Cell Biochem 107:58–64
Qian BZ et al (2011) CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature 475:222–225
Garber K (2009) First results for agents targeting cancer-related inflammation. J Natl Cancer Inst 101:1110–1112
Berek JS (2004) Immunotherapy of ovarian cancer with antibodies: a focus on oregovomab. Expert Opin Biol Ther 4:1159–1165
Ehlen TG et al (2005) A pilot phase 2 study of oregovomab murine monoclonal antibody to CA125 as an immunotherapeutic agent for recurrent ovarian cancer. Int J Gynecol Cancer 15:1023–1034
Bayes M, Rabasseda X, Prous JR (2007) Gateways to clinical trials. Methods Find Exp Clin Pharmacol 29:53–71
Berek J et al (2009) Oregovomab maintenance monoimmunotherapy does not improve outcomes in advanced ovarian cancer. J Clin Oncol 27:418–425
Teng L, Xie J, Lee RJ (2012) Clinical translation of folate receptor-targeted therapeutics. Expert Opin Drug Deliv 9(8):901–908
Jelovac D, Armstrong DK (2012) Role of Farletuzumab in epithelial ovarian carcinoma. Curr Pharm Des 18(25):3812–5
Pegram MD et al (2009) Phase I dose escalation pharmacokinetic assessment of intravenous humanized anti-MUC1 antibody AS1402 in patients with advanced breast cancer. Breast Cancer Res 11:R73
Beatson RE, Taylor-Papadimitriou J, Burchell JM (2010) MUC1 immunotherapy. Immunotherapy 2:305–327
Oei AL et al (2008) Induction of IgG antibodies to MUC1 and survival in patients with epithelial ovarian cancer. Int J Cancer 123:1848–1853
Ibrahim NK et al (2011) Randomized phase II trial of letrozole plus anti-MUC1 antibody AS1402 in hormone receptor-positive locally advanced or metastatic breast cancer. Clin Cancer Res 17:6822–6830
Apostolopoulos V et al (2006) Pilot phase III immunotherapy study in early-stage breast cancer patients using oxidized mannan-MUC1 [ISRCTN71711835]. Breast Cancer Res 8:R27
Bell-McGuinn KM et al (2011) A phase II, single-arm study of the anti-alpha5beta1 integrin antibody volociximab as monotherapy in patients with platinum-resistant advanced epithelial ovarian or primary peritoneal cancer. Gynecol Oncol 121:273–279
Carter A (2010) Integrins as target: first phase III trial launches, but questions remain. J Natl Cancer Inst 102:675–677
Almokadem S, Belani CP (2012) Volociximab in cancer. Expert Opin Biol Ther 12:251–257
Kuwada SK (2007) Drug evaluation: volociximab, an angiogenesis-inhibiting chimeric monoclonal antibody. Curr Opin Mol Ther 9:92–98
Tolcher AW et al (2007) Phase I pharmacokinetic and biologic correlative study of mapatumumab, a fully human monoclonal antibody with agonist activity to tumor necrosis factor-related apoptosis-inducing ligand receptor-1. J Clin Oncol 25:1390–1395
Leong S et al (2009) Mapatumumab, an antibody targeting TRAIL-R1, in combination with paclitaxel and carboplatin in patients with advanced solid malignancies: results of a phase I and pharmacokinetic study. J Clin Oncol 27:4413–4421
Younes A et al (2010) A Phase 1b/2 trial of mapatumumab in patients with relapsed/refractory non-Hodgkin’s lymphoma. Br J Cancer 103:1783–1787
Trarbach T et al (2010) Phase II trial of mapatumumab, a fully human agonistic monoclonal antibody that targets and activates the tumour necrosis factor apoptosis-inducing ligand receptor-1 (TRAIL-R1), in patients with refractory colorectal cancer. Br J Cancer 102:506–512
Hersey P et al (2010) A randomized phase 2 study of etaracizumab, a monoclonal antibody against integrin alpha(v)beta(3), + or − dacarbazine in patients with stage IV metastatic melanoma. Cancer 116:1526–1534
Delbaldo C et al (2008) Phase I and pharmacokinetic study of etaracizumab (Abegrin), a humanized monoclonal antibody against alphavbeta3 integrin receptor, in patients with advanced solid tumors. Invest New Drugs 26:35–43
Chong G et al (2006) Phase III trial of 5-fluorouracil and leucovorin plus either 3 H1 anti-idiotype monoclonal antibody or placebo in patients with advanced colorectal cancer. Ann Oncol 17:437–442
Meyer T et al (2009) A phase I trial of radioimmunotherapy with 131I-A5B7 anti-CEA antibody in combination with combretastatin-A4-phosphate in advanced gastrointestinal carcinomas. Clin Cancer Res 15:4484–4492
Shibata S et al (2009) A phase I study of a combination of yttrium-90-labeled anti-carcinoembryonic antigen (CEA) antibody and gemcitabine in patients with CEA-producing advanced malignancies. Clin Cancer Res 15:2935–2941
Govindan SV, Cardillo TM, Moon SJ, Hansen HJ, Goldenberg DM (2009) CEACAM5-targeted therapy of human colonic and pancreatic cancer xenografts with potent labetuzumab-SN-38 immunoconjugates. Clin Cancer Res 15:6052–6061
Schmidt M et al (2012) Phase IB study of the EpCAM antibody adecatumumab combined with docetaxel in patients with EpCAM-positive relapsed or refractory advanced-stage breast cancer. Ann Oncol 23:2306–13
Hassan R, Bera T, Pastan I (2004) Mesothelin: a new target for immunotherapy. Clin Cancer Res 10:3937–3942
Hassan R et al (2010) Phase I clinical trial of the chimeric anti-mesothelin monoclonal antibody MORAb-009 in patients with mesothelin-expressing cancers. Clin Cancer Res 16:6132–6138
Liu R, Li H, Liu L, Yu J, Ren X (2012) Fibroblast activation protein: a potential therapeutic target in cancer. Cancer Biol Ther 13:123–129
Scott AM et al (2003) A Phase I dose-escalation study of sibrotuzumab in patients with advanced or metastatic fibroblast activation protein-positive cancer. Clin Cancer Res 9:1639–1647
Balkwill FR, Mantovani A (2012) Cancer-related inflammation: common themes and therapeutic opportunities. Semin Cancer Biol 22:33–40
Lust JA et al (2009) Induction of a chronic disease state in patients with smoldering or indolent multiple myeloma by targeting interleukin 1{beta}-induced interleukin 6 production and the myeloma proliferative component. Mayo Clin Proc 84:114–122
Dodson S et al (2010) Muscle wasting in cancer cachexia: clinical implications, diagnosis, and emerging treatment strategies. Annu Rev Med 62:265–279
Maccio A et al (2012) A randomized phase III clinical trial of a combined treatment for cachexia in patients with gynecological cancers: evaluating the impact on metabolic and inflammatory profiles and quality of life. Gynecol Oncol 124:417–425
Madeddu C et al (2012) Randomized phase III clinical trial of a combined treatment with carnitine + celecoxib +/− megestrol acetate for patients with cancer-related anorexia/cachexia syndrome. Clin Nutr 31:176–182
Rech AJ et al (2012) CD25 blockade depletes and selectively reprograms regulatory T-cells and cooperates with immunotherapy in cancer patients. Sci Transl Med 4(134):134ra62
Balkwill F (2009) Tumour necrosis factor and cancer. Nat Rev Cancer 9:361–371
Acknowledgements
Thanks to our colleagues for many informative discussions. This work was supported by CA105207, CA054174, FD003118, the Fanny Rippel Foundation, the Voelcker Trust, the Hayes Endowment, The Holly Beach Public Library Association, The Owens Foundation, The Hogg Foundation and UTHSCSA endowments.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media New York
About this chapter
Cite this chapter
Mahalingam, D., Curiel, T.J. (2013). Antibodies as Cancer Immunotherapy. In: Curiel, T. (eds) Cancer Immunotherapy. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4732-0_11
Download citation
DOI: https://doi.org/10.1007/978-1-4614-4732-0_11
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-4731-3
Online ISBN: 978-1-4614-4732-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)