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Monoclonal Antibodies as Treatment Modalities in Head and Neck Cancers

  • Received: 29 August 2015 Accepted: 28 October 2015 Published: 03 November 2015
  • The standard treatments of surgery, radiation, and chemotherapy in head and neck squamous cell carcinomas (HNSCC) causes disturbance to normal surrounding tissues, systemic toxicities and functional problems with eating, speaking, and breathing. With early detection, many of these cancers can be effectively treated, but treatment should also focus on retaining the function of the proximal nerves, tissues and vasculature surrounding the tumor. With current research focused on understanding pathogenesis of these cancers in a molecular level, targeted therapy using monoclonal antibodies (MoAbs), can be modified and directed towards tumor genes, proteins and signal pathways with the potential to reduce unfavorable side effects of current treatments. This review will highlight the current MoAb therapies used in HNSCC, and discuss ongoing research efforts to develop novel treatment agents with potential to improve efficacy, increase overall survival (OS) rates and reduce toxicities.

    Citation: Vivek Radhakrishnan, Mark S. Swanson, Uttam K. Sinha. Monoclonal Antibodies as Treatment Modalities in Head and Neck Cancers[J]. AIMS Medical Science, 2015, 2(4): 347-359. doi: 10.3934/medsci.2015.4.347

    Related Papers:

  • The standard treatments of surgery, radiation, and chemotherapy in head and neck squamous cell carcinomas (HNSCC) causes disturbance to normal surrounding tissues, systemic toxicities and functional problems with eating, speaking, and breathing. With early detection, many of these cancers can be effectively treated, but treatment should also focus on retaining the function of the proximal nerves, tissues and vasculature surrounding the tumor. With current research focused on understanding pathogenesis of these cancers in a molecular level, targeted therapy using monoclonal antibodies (MoAbs), can be modified and directed towards tumor genes, proteins and signal pathways with the potential to reduce unfavorable side effects of current treatments. This review will highlight the current MoAb therapies used in HNSCC, and discuss ongoing research efforts to develop novel treatment agents with potential to improve efficacy, increase overall survival (OS) rates and reduce toxicities.



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    [1] American Cancer Society. Cancer Facts & Figures 2015. Atlanta: American Cancer Society; 2015.
    [2] Rousseau A, Badoual C (2011) Squamous cell carcinoma: an overvie Atlas Genet Cytogenet Oncol Haematol. Head and Neck, in press.
    [3] Schantz SP, Harrison LB, Forastiere A (2001) Tumors of the nasal cavity and paranasal sinuses, nasopharynx, oral cavity, and oropharynx. In: DeVita VT, Hellman SA, Rosenberg SA, eds. Cancer: principles and practice of oncology. 6th ed. Philadelphia: Lippincott Williams & Wilkins: 797-860.
    [4] Rubin Grandis J, Melhem MF, Gooding WE, et al. (1988) Levels of TGF-alpha and EGFR protein in head and neck squamous cell carcinoma and patient survival. J Natl Cancer Inst 90: 824-832.
    [5] Chung CH, Ely K, McGavran L, et al. (2006) Increased epidermal growth factor receptor gene copy number is associated with poor prognosis in head and neck squamous cell carcinomas. J Clin Oncol 24: 4170-4176.
    [6] Temam S, Kawaguchi H, El-Naggar AK, et al. (2007) Epidermal growth factor receptor copy number alterations correlate with poor clinical outcome in patients with head and neck squamous cancer. J Clin Oncol 25: 2164-2170. doi: 10.1200/JCO.2006.06.6605
    [7] Bonner JA, Harari PM, Giralt J (2006) Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354: 567-578. doi: 10.1056/NEJMoa053422
    [8] Goldstein NI, Prewett M, Zuklys K, et al. (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.
    [9] Li S, Schmitz KR, Jeffrey PD, et al. (2005) Structural basis for inhibition of the epidermal growth factor receptor by cetuximab. Cancer Cell 7: 301-311. doi: 10.1016/j.ccr.2005.03.003
    [10] Sato JD, Kawamoto T, Le AD, et al. (1983) Biological effects in vitro of monoclonal antibodies to human epidermal growth factor receptors. Mol Biol Med 1: 511-529.
    [11] Kang X, Patel D, Ng S, et al. (2007) High affinity Fc receptor binding and potent induction of antibody-dependent cellular cytotoxicity (ADCC) in vitro by anti-epidermal growth factor receptor antibody cetuximab. J Clin Oncol 25: 128s.
    [12] Kimura H, Sakai K, Arao T, et al. (2007) Antibody-dependent cellular cytotoxicity of cetuximab against tumor cells with wild-type or mutant epidermal growth factor receptor. Cancer Sci 98: 1275-1280.
    [13] Zhang W, Gordon M, Schultheis AM, et al. (2007) FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab. J Clin Oncol 25: 3712-3718. doi: 10.1200/JCO.2006.08.8021
    [14] Fan Z, Baselga J, Masui H, et al. (1993) Antitumor effect of anti-epidermal growth factor receptor monoclonal antibodies plus cis-diamminedichloroplatinum on well established A431 cell xenografts. Cancer Res 53: 4637-4642.
    [15] Burtness B, Goldwasser MA, Flood W, 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 doi: 10.1200/JCO.2005.02.4646
    [16] Thomas KH, Patrick JS (2013) Antigen-specific immunotherapy in head and neck cancer. Adv Cell Mol Otolaryngol 1.
    [17] Ira Mellman, George Coukos, Glenn Dranoff (2011) Cancer immunotherapy comes of age. Nature 480: 480-489.
    [18] Andrew MS, James PA, Jedd DW (2012) Monoclonal antibodies in cancer therapy. Cancer Immun 12: 14.
    [19] Brahmer JR, Drake CG, Wollner I, et al. (2010) Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics and immunologic correlates. J Clin Oncol 28: 3167-3175. doi: 10.1200/JCO.2009.26.7609
    [20] Hodi FS, O'Day SJ, McDermott DF, et al. (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363: 711-723. doi: 10.1056/NEJMoa1003466
    [21] Suntharalingam, G, Perry MR, Ward S, et al. (2006) Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N Engl J Med 355: 1018-1028. doi: 10.1056/NEJMoa063842
    [22] Brahmer JR, Drake CG, Wollner I, et al. (2010). Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics and immunologic correlates. J Clin Oncol 28: 3167-3175. doi: 10.1200/JCO.2009.26.7609
    [23] Keir ME, Butte MJ, Freeman GJ, et al. (2008) PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 26: 677-704 doi: 10.1146/annurev.immunol.26.021607.090331
    [24] Parsa AT, Waldron JS, Panner A, et al. (2006) Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma. Nature Med 13: 84-88.
    [25] Gadiot J, Hooijkaas AI, Kaiser AD, et al. (2011) Overall survival and PD-L1 expression in metastasized malignant melanoma. Cancer 117: 2192-2201. doi: 10.1002/cncr.25747
    [26] Gao Q, Wang XY, Qiu SJ, et al. (2009) Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma. Clin Cancer Res 15: 971-979.
    [27] Leach DR, Krummel MF, Allison JP (1996) Enhancement of antitumor immunity by CTLA-4. Science 271: 1734-1736. doi: 10.1126/science.271.5256.1734
    [28] Van Cutsem E, Köhne CH, Hitre E, et al. (2009) Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 360: 1408-1417.
    [29] Schliemann C, Neri D (2010) Antibody-based vascular tumor targeting. Cancer Res 180: 201-216.
    [30] Pillay V, Gan HK, Scott AM (2011) Antibodies in oncology. N Biotechnol 28: 518-529. doi: 10.1016/j.nbt.2011.03.021
    [31] Divgi CR, Welt S, Kris M, et al. (1991) Phase I and imaging trial of indium 111-labeled anti-epidermal growth factor receptor monoclonal antibody 225 in patients with squamous cell lung carcinoma. J Natl Cancer Inst 83: 97-104. doi: 10.1093/jnci/83.2.97
    [32] Ellis LM, Hicklin DJ (2008) VEGF-targeted therapy: mechanisms of anti-tumor activity. Nat Rev Cancer 8: 579-591. doi: 10.1038/nrc2403
    [33] Friedman HS, Prados MD, Wen PY, et al. (2009) Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 27: 4733-4740. doi: 10.1200/JCO.2008.19.8721
    [34] Heiss MM, Murawa P, Koralewski P, et al. (2010) The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: results of a prospective randomized phase II/III trial. Int J Cancer 127: 2209-2221. doi: 10.1002/ijc.25423
    [35] Boland WK, Bebb G. (2009) Nimotuzumab: a novel anti-EGFR monoclonal antibody that retains anti-EGFR activity while minimizing skin toxicity. Expert Opin Biol Ther 9:1199-1206.
    [36] Curran D, Giralt J, Harari PM, et al. (2007) Quality of life in head and neck cancer patients after treatment with high-dose radiotherapy alone or in combination with cetuximab. J Clin Oncol 25: 2191-2197. doi: 10.1200/JCO.2006.08.8005
    [37] Bonner JA, Harari PM, Giralt J, et al. (2010) Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomized trial, and relation between cetuximab-induced rash and survival. Lancet Oncol 11: 21-28. doi: 10.1016/S1470-2045(09)70311-0
    [38] Koutcher L, Sherman E, Fury M, et al. (2011) Concurrent cisplatin and radiation versus cetuximab and radiation for locally advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys 81: 915-922. doi: 10.1016/j.ijrobp.2010.07.008
    [39] Chew A, Hay J, Laskin JJ, et al. (2011) Toxicity in combined modality treatment of HNSCC: Cisplatin versus cetuximab. J Clin Oncol 29: 5526.
    [40] Shapiro LQ, Sherman EJ, Koutcher L, et al. (2012) Efficacy of concurrent cetuximab (C225) versus 5-fluorouracil/carboplatin (5FU/CBDCA) or cisplatin (CDDP) with intensity-modulated radiation therapy (IMRT) for locally advanced head and neck cancer (LAHNSCC). J Clin Oncol 30: 5537.
    [41] Pryor DI, Porceddu SV, Burmeister BH, et al. (2009) Enhanced toxicity with concurrent cetuximab and radiotherapy in head and neck cancer. Radiother Oncol 90: 172-176. doi: 10.1016/j.radonc.2008.09.018
    [42] Vermorken JB, Mesia R, Rivera F, et al. (2008) Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 359: 1116-1127. doi: 10.1056/NEJMoa0802656
    [43] Hitt R, Irigoyen A, Cortes-Funes H, et al. (2012). Spanish Head and Neck Cancer Cooperative Group (TTCC) Phase II study of the combination of cetuximab and weekly paclitaxel in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of head and neck. Ann Oncol 23: 1016-1022. doi: 10.1093/annonc/mdr367
    [44] Ang KK, Zhang QE, Rosenthal DI, et al. (2011) A randomized phase III trial (RTOG 0522) of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III-IV head and neck squamous cell carcinomas (HNC). J Clin Oncol 30: 360.
    [45] Ley J, Mehan P, Wildes TM, et al. (2012) Concurrent cisplatin vs. cetuximab with definitive radiation therapy (RT) for head and neck squamous cell carcinoma (HNSCC): A retrospective comparison. Multidisciplinary Head and Neck Cancer Symposium (Phoenix, AZ)
    [46] Balz V, Scheckenbach K, Gotte K, et al. (2003) Is the p53 inactivation frequency in squamous cell carcinomas of the head and neck underestimated? Analysis of p53 exons 2-11 and human papillomavirus 16/18 E6 transcripts in 123 unselected tumor specimens. Cancer Res 63: 1188-1191.
    [47] Deleo AB (1998) p53-based immunotherapy of cancer. Crit Rev Immunol 18: 29-35. doi: 10.1615/CritRevImmunol.v18.i1-2.40
    [48] Hoffmann TK, Nakano K, Elder EM, et al. (2000) Generation of T cells specific for the wild-type sequence p53(264-272) peptide in cancer patients: Implications for immunoselection of epitope loss variants. J Immunol 165: 5938-5944. doi: 10.4049/jimmunol.165.10.5938
    [49] Andrade FPA, Ito D, Deleo AB, et al. (2010) CD8+ T cell recognition of polymorphic wild-type sequence p53(65-73) peptides in squamous cell carcinoma of the head and neck. Cancer Immunol Immunother 59: 1561-1568. doi: 10.1007/s00262-010-0886-1
    [50] Chikamatsu K, Albers A, Stanson J, et al. (2003) P53(110-124)-specific human CD4+ T-helper cells enhance in vitro generation and antitumor function of tumor-reactive CD8+ T cells. Cancer Res 63: 3675-3681.
    [51] Albers AE, Ferris RL, Kim GG, et al. (2005) Immune responses to p53 in patients with cancer: Enrichment in tetramer+p53 peptide-specific T cells and regulatory T cells at tumor sites. Cancer Immunol Immunother 54: 1072-1081. doi: 10.1007/s00262-005-0670-9
    [52] Zhang Y, Sturgis EM, Huang Z, et al. (2012) Genetic variants of the p53 and p73 genes jointly increase risk of second primary malignancies in patients after index squamous cell carcinoma of the head and neck. Cancer 118: 485-492. doi: 10.1002/cncr.26222
    [53] Clayman GL, El-Naggar AK, Lippman SM, et al. (1998) Adenovirus-mediated p53 gene transfer in patients with advanced recurrent head and neck squamous cell carcinoma. J Clin Oncol 16: 2221-2232.
    [54] Heusinkveld M, Goedemans R, Briet RJ, et al. (2012) Systemic and local human papillomavirus 16-specific T-cell immunity in patients with head and neck cancer. Int J Cancer 131: E74-85. doi: 10.1002/ijc.26497
    [55] Wansom D, Light E, Worden F, et al. (2010) Correlation of cellular immunity with human papillomavirus 16 status and outcome in patients with advanced oropharyngeal cancer. Arch Otolaryngol Head Neck Surg 136: 1267-1273. doi: 10.1001/archoto.2010.211
    [56] The Cancer Genome Atlas Network, 2015. Comprehensive Genomic Characterization of Head and Neck Squamous Cell Carcinomas. Nature 517: 576-582.
    [57] Wei G, John ZHL, Jimmy YWC, et al. (2012) mTOR pathway and mTOR inhibitors in head and neck cancer department of surgery. Otolaryngology.
    [58] Hay N, Sonenberg N (2004) Upstream and downstream of mTOR. Genes Dev 18: 1926-1945. doi: 10.1101/gad.1212704
    [59] Lionello SM, Loreggian BL (2012) High mTOR expression is associated with a worse oncological outcome in laryngeal carcinoma treated with postoperative radiotherapy: a pilot study. J Oral Pathol Med 41: 136-140. doi: 10.1111/j.1600-0714.2011.01083.x
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