Immunotherapy of head and neck cancer: current and future considerations

Alexander D Rapidis, Gregory T Wolf, Alexander D Rapidis, Gregory T Wolf

Abstract

Patients with head and neck squamous cell carcinoma (HNSCC) are at considerable risk for death, with 5-year relative survival rates of approximately 60%. The profound multifaceted deficiencies in cell-mediated immunity that persist in most patients after treatment may be related to the high rates of treatment failure and second primary malignancies. Radiotherapy and chemoradiotherapy commonly have severe acute and long-term side effects on immune responses. The development of immunotherapies reflects growing awareness that certain immune system deficiencies specific to HNSCC and some other cancers may contribute to the poor long-term outcomes. Systemic cell-mediated immunotherapy is intended to activate the entire immune system and mount a systemic and/or locoregional antitumor response. The delivery of cytokines, either by single cytokines, for example, interleukin-2, interleukin-12, interferon-gamma, interferon-alpha, or by a biologic mix of multiple cytokines, such as IRX-2, may result in tumor rejection and durable immune responses. Targeted immunotherapy makes use of monoclonal antibodies or vaccines. All immunotherapies for HNSCC except cetuximab remain investigational, but a number of agents whose efficacy and tolerability are promising have entered phase 2 or phase 3 development.

References

    1. American Cancer Society. Cancer Facts & Figures 2008. Atlanta, Ga, USA: American Cancer Society; 2008.
    1. Cann CI, Fried MP, Rothman KJ. Epidemiology of squamous cell cancer of the head and neck. Otolaryngologic Clinics of North America. 1985;18(3):367–388.
    1. Ries L, Melbert D, Drapcho M, et al. SEER Cancer Statistics Review, National Cancer Institute, November 2008, .
    1. Haddad RI, Shin DM. Recent advances in head and neck cancer. New England Journal of Medicine. 2008;359(11):1143–1154.
    1. Lippman S, Hong WK. Retinoid chemoprevention of upper aerodigestive tract carcinogenesis. In: DeVita V, Hellman S, Rosenberg S, editors. Important Advances in Oncology. Philadelphia, Pa, USA: J. B. Lippincott; 1992. pp. 93–109.
    1. Brachman DG, Graves D, Vokes E, et al. Occurrence of p53 gene deletions and human papilloma virus infection in human head and neck cancer. Cancer Research. 1992;52(17):4832–4836.
    1. Gillison ML, Shah KV. Human papillomavirus-associated head and neck squamous cell carcinoma: mounting evidence for an etiologic role for human papillomavirus in a subset of head and neck cancers. Current Opinion in Oncology. 2001;13(3):183–188.
    1. D'Souza G, Kreimer AR, Viscidi R, et al. Case-control study of human papillomavirus and oropharyngeal cancer. New England Journal of Medicine. 2007;356(19):1944–1956.
    1. Alhamarneh O, Amarnath SM, Stafford ND, Greenman J. Regulatory T cells: what role do they play in antitumor immunity in patients with head and neck cancer? Head Neck. 2008;30:251–261.
    1. National Comprehensive Cancer Network. Head and Neck Cancers: National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology, version 2, November 2008, .
    1. Schmid DT, Stoeckli SJ, Bandhauer F, et al. Impact of positron emission tomography on the initial staging and therapy in locoregional advanced squamous cell carcinoma of the head and neck. Laryngoscope. 2003;113(5):888–891.
    1. Deschler DG, Day T, editors. Pocket Guide to TNM Staging of Head and Neck Cancer and Neck Dissection Classification. 3rd edition. Alexandria, Va, USA: American Academy of Otolaryngology—Head and Neck Surgery Foundation; 2008.
    1. Seiwert TY, Cohen EE. State-of-the-art management of locally advanced head and neck cancer. British Journal of Cancer. 2005;92(8):1341–1348.
    1. Haddad R, Wirth L, Posner M. Emerging drugs for head and neck cancer. Expert Opinion on Emerging Drugs. 2006;11(3):461–467.
    1. Erbitux® (cetuximab) Prescribing Information. New York, NY, USA: ImClone Systems Incorporated; 2008.
    1. Lee SC, López-Albaitero A, Ferris RL. Immunotherapy of head and neck cancer using tumor antigen-specific monoclonal antibodies. Current Oncology Reports. 2009;11(2):156–162.
    1. Kies MS. New treatments in head and neck cancer. Clinical Advances in Hematology and Oncology. 2005;3(2):92–93.
    1. Whiteside TL. Immunobiology and immunotherapy of head and neck cancer. Current Oncology Reports. 2001;3(1):46–55.
    1. Grandis JR, Falkner DM, Melhem MF, Gooding WE, Drenning SD, Morel PA. Human leukocyte antigen class I allelic and haplotype loss in squamous cell carcinoma of the head and neck: clinical and immunogenetic consequences. Clinical Cancer Research. 2000;6(7):2794–2802.
    1. Mandic R, Lieder A, Sadowski M, Peldszus R, Werner JA. Comparison of surface HLA class I levels in squamous cell carcinoma cell lines of the head and neck. Anticancer Research. 2004;24(2B):973–979.
    1. Kim JW, Wieckowski E, Taylor DD, Reichert TE, Watkins S, Whiteside TL. Fas ligand-positive membranous vesicles isolated from sera of patients with oral cancer induce apoptosis of activated T lymphocytes. Clinical Cancer Research. 2005;11(3):1010–1020.
    1. Cross DS, Platt JL, Juhn SK, Bach FH, Adams GL. Administration of a prostaglandin synthetase inhibitor associated with an increased immune cell infiltrate in squamous cell carcinoma of the head and neck. Archives of Otolaryngology. 1992;118(5):526–528.
    1. Gabrilovich DI, Chen HL, Girgis KR, et al. Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nature Medicine. 1996;2(10):1096–1103.
    1. Young MR. Protective mechanisms of head and neck squamous cell carcinomas from immune assault. Head and Neck. 2006;28(5):462–470.
    1. Hadden JW. Immunodeficiency and cancer: prospects for correction. International Immunopharmacology. 2003;3(8):1061–1071.
    1. Young MR. Trials and tribulations of immunotherapy as a treatment option for patients with squamous cell carcinoma of the head and neck. Cancer Immunology, Immunotherapy. 2004;53(5):375–382.
    1. Dunn G, Oliver KM, Loke D, Stafford ND, Greenman J. Dendritic cells and HNSCC: a potential treatment option? Oncology Reports. 2005;13(1):3–10.
    1. Meneses A, Verastegui E, Barrera JL, de la Garza J, Hadden JW. Lymph node histology in head and neck cancer: impact of immunotherapy with IRX-2. International Immunopharmacology. 2003;3(8):1083–1091.
    1. Reichert TE, Scheuer C, Day R, Wagner W, Whiteside TL. The number of intratumoral dendritic cells and zeta-chain expression in T cells as prognostic and survival biomarkers in patients with oral carcinoma. Cancer. 2001;91(11):2136–2147.
    1. Young MR, Petruzzelli GJ, Kolesiak K, Achille N, Lathers DM, Gabrilovich DI. Human squamous cell carcinomas of the head and neck chemoattract immune suppressive CD34+ progenitor cells. Human Immunology. 2001;62(4):332–341.
    1. Wu AA, Niparko KJ, Pai SI. Immunotherapy for head and neck cancer. Journal of Biomedical Science. 2008;15(3):275–289.
    1. Zhang L, Conejo-Garcia JR, Katsaros D, et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. New England Journal of Medicine. 2003;348(3):203–213.
    1. Haanen JB, Baars A, Gomez R, et al. Melanoma-specific tumor-infiltrating lymphocytes but not circulating melanoma-specific T cells may predict survival in resected advanced-stage melanoma patients. Cancer Immunology, Immunotherapy. 2006;55(4):451–458.
    1. Wolf GT, Schmaltz S, Hudson J, et al. Alterations in T-lymphocyte subpopulations in patients with head and neck cancer: correlations with prognosis. Archives of Otolaryngology. 1987;133(11):1200–1206.
    1. Comoli P, Pedrazzoli P, Maccario R, et al. Cell therapy of stage IV nasopharyngeal carcinoma with autologous Epstein-Barr virus-targeted cytotoxic T lymphocytes. Journal of Clinical Oncology. 2005;23(35):8942–8949.
    1. Chang AE, Li Q, Jiang G, Teknos TN, Chepeha DB, Bradford CR. Generation of vaccine-primed lymphocytes for the treatment of head and neck cancer. Head and Neck. 2003;25(3):198–209.
    1. To WC, Wood BG, Krauss JC, et al. Systemic adoptive T-cell immunotherapy in recurrent and metastatic carcinoma of the head and neck: a phase 1 study. Archives of Otolaryngology. 2000;126(10):1225–1231.
    1. Artusio E, Hathaway B, Stanson J, Whiteside TL. Transfection of human monocyte-derived dendritic cells with native tumor DNA induces antigen-specific T-cell responses in vitro. Cancer Biology and Therapy. 2006;5(12):1624–1631.
    1. Moyer JS, Li J, Wei S, Teitz-Tennenbaum S, Chang AE. Intratumoral dendritic cells and chemoradiation for the treatment of murine squamous cell carcinoma. Journal of Immunotherapy. 2008;31(9):885–895.
    1. National Institutes of Health. , November 2008, .
    1. Hu JC, Coffin RS, Davis CJ, et al. A phase I study of OncoVEXGM-CSF, a second-generation oncolytic herpes simplex virus expressing granulocyte macrophage colony-stimulating factor. Clinical Cancer Research. 2006;12(22):6737–6747.
    1. Coffin RS, Hingorani M, McNeish I, et al. Phase I/II trial of OncoVEXGM-CSF combined with radical chemoradiation (CRT) in patients with newly diagnosed node-positive stage III/IV head and neck cancer (HNC) Journal of Clinical Oncology. 2007;25(18S):p. 14095.
    1. Grande C, Firvida JL, Navas V, Casal J. Interleukin-2 for the treatment of solid tumors other than melanoma and renal cell carcinoma. Anti-Cancer Drugs. 2006;17(1):1–12.
    1. O'Malley BW, Jr., Li D, McQuone SJ, Ralston R. Combination nonviral interleukin-2 gene immunotherapy for head and neck cancer: from bench top to bedside. Laryngoscope. 2005;115(3):391–404.
    1. De Stefani A, Forni G, Ragona R, et al. Improved survival with perilymphatic interleukin 2 in patients with resectable squamous cell carcinoma of the oral cavity and oropharynx. Cancer. 2002;95(1):90–97.
    1. Richtsmeier WJ, Koch WW, McGuire WP, Poole ME, Chang EH. Phase I-II study of advanced head and neck squamous cell carcinoma patients treated with recombinant human interferon gamma. Archives of Otolaryngology. 1990;116(11):1271–1277.
    1. Bazarbashi S, Rahal M, Raja MA, et al. A pilot trial of combination cisplatin, 5-fluorouracil, and interferon-alpha in the treatment of advanced esophageal carcinoma. Chemotherapy. 2002;48(4):211–216.
    1. Seixas-Silva JA, Jr., Richards T, Khuri FR, et al. Phase 2 bioadjuvant study of interferon alfa-2a, isotretinoin, and vitamin E in locally advanced squamous cell carcinoma of the head and neck: long-term follow-up. Archives of Otolaryngology. 2005;131(4):304–307.
    1. Urba SG, Forastiere AA, Wolf GT, Amrein PC. Intensive recombinant interleukin-2 and alpha-interferon therapy in patients with advanced head and neck squamous carcinoma. Cancer. 1993;71(7):2326–2331.
    1. Van Herpen CM, Looman M, Zonneveld M, et al. Intratumoral administration of recombinant human interleukin 12 in head and neck squamous cell carcinoma patients elicits a T-Helper 1 profile in the locoregional lymph nodes. Clinical Cancer Research. 2004;10(8):2626–2635.
    1. Egan JE, Quadrini KJ, Santiago-Schwarz F, Hadden JW, Brandwein HJ, Signorelli KL. IRX-2, a novel in vivo immunotherapeutic, induces maturation and activation of human dendritic cells in vitro. Journal of Immunotherapy. 2007;30(6):624–633.
    1. Meneses A, Verastegui E, Barrera JL, Zinser J, de la Garza J, Hadden JW. Histologic findings in patients with head and neck squamous cell carcinoma receiving perilymphatic natural cytokine mixture (IRX-2) prior to surgery. Archives of Pathology and Laboratory Medicine. 1998;122:447–454.
    1. Whiteside TL, Czystowska M, Szczepanski M, et al. Overcoming the immunosuppressive effects of head and neck cancer. In: Proceedings of the 7th International Conference on Head and Neck Cancer of the American Head and Neck Society; July 2008; San Francisco, Calif, USA.
    1. Wolf GT, Fee WE, Dolan R, et al. IRX-2: promising new immunotherapy for head and neck cancer. In: Proceedings of the 7th International Conference on Head and Neck Cancer of the American Head and Neck Society; July 2008; San Francisco, Calif, USA.
    1. Moyer J, Wolf GT, Fee WE, et al. Overcoming the immunosuppression of head and neck cancer with IRX-2 (citoplurikin). In: Proceedings of the 26th Chemotherapy Foundation Symposium; November 2008; New York, NY, USA.
    1. Rauch J, Ahlemann M, Schaffrik M, et al. Allogenic antibody-mediated identification of head and neck cancer antigens. Biochemical and Biophysical Research Communications. 2004;323(1):156–162.
    1. Eura M, Ogi K, Chikamatsu K, et al. Expression of the MAGE gene family in human head-and-neck squamous-cell carcinomas. International Journal of Cancer. 1995;64(5):304–308.
    1. Kienstra MA, Neel HB, Strome SE, Roche P. Identification of NY-ESO-1, MAGE-1, and MAGE-3 in head and neck squamous cell carcinoma. Head and Neck. 2003;25(6):457–463.
    1. Chen Y-T, Scanlan MJ, Sahin U, et al. A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. In: Proceedings of the National Academy of Sciences of the United States of America, vol. 94; March 1997; pp. 1914–1918.
    1. Clark CE, Vonderheide RH. Cancer-testis antigens in tumor biology and immunotherapy. Cancer Biology and Therapy. 2006;5(9):1226–1227.
    1. Balz V, Scheckenbach K, Götte K, Bockmühl U, Petersen I, Bier H. 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 Research. 2003;63(6):1188–1191.
    1. Albers A, Abe K, Hunt J, et al. Antitumor activity of human papillomavirus type 16 E7-specific T cells against virally infected squamous cell carcinoma of the head and neck. Cancer Research. 2005;65(23):11146–11155.
    1. Devaraj K, Gillison ML, Wu T-C. Development of HPV vaccines for HPV-associated head and neck squamous cell carcinoma. Critical Reviews in Oral Biology and Medicine. 2003;14(5):345–362.
    1. Gillison ML, Koch WM, Capone RB, et al. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. Journal of the National Cancer Institute. 2000;92(9):709–720.
    1. Wakeling AE. Epidermal growth factor receptor tyrosine kinase inhibitors. Current Opinion in Pharmacology. 2002;2(4):382–387.
    1. Rapidis AD, Vermorken JB, Bourhis J. Targeted therapies in head and neck cancer: past, present, and future. Reviews on Recent Clinical Trials. 2008;3(3):156–166.
    1. Trarbach T, Schleucher N, Weber D, et al. Phase I study of the humanized antiepidermal growth factor receptor (EGFR) antibody ED 72000 (matuzumab) in combination with cisplatin, 5-fluorouracil, and leucovorin (PFL) in patients (pts) with advanced esophagogastric (EG) adenocarcinoma. Journal of Clinical Oncology. 2005;23:p. 3156.
    1. Figlin R, Belldegrun A, Crawford J. ABX-EGF, a fully humanized antiepidermal growth factor receptor monoclonal antibody (mAB) in patients with advanced cancer: phase I clinical results. Journal of Clinical Oncology. 2002;21:p. 35.
    1. Modjtahedi H, Hickish T, Nicolson M, et al. Phase I trial and tumour localisation of the anti-EGFR monoclonal antibody ICR62 in head and neck or lung cancer. British Journal of Cancer. 1996;73(2):228–235.
    1. Crombet T, Osorio M, Cruz T, et al. Use of the humanized antiepidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy in the treatment of locally advanced head and neck cancer patients. Journal of Clinical Oncology. 2004;22(9):1646–1654.
    1. Johns TG, Mellman I, Cartwright GA, et al. The antitumor monoclonal antibody 806 recognizes a high-mannose form of the EGF receptor that reaches the cell surface when cells overexpress the receptor. FASEB Journal. 2005;19(7):780–782.
    1. Presta LG, Chen H, O'Connor SJ, et al. Humanization of an antivascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Research. 1997;57(20):4593–4599.
    1. O-Charoenrat P, Rhys-Evans P, Modjtahedi H, Eccles S. Vascular endothelial growth factor family members are differentially regulated by c-erbB signaling in head and neck squamous carcinoma cells. Clinical and Experimental Metastasis. 2000;18(2):155–161.
    1. Kyzas PA, Stefanou D, Batistatou A, Agnantis NJ. Prognostic significance of VEGF immunohistochemical expression and tumor angiogenesis in head and neck squamous cell carcinoma. Journal of Cancer Research and Clinical Oncology. 2005;131(9):624–630.
    1. Karamouzis M, Friedland D, Johnson R, Rajasenan K, Branstetter B, Argiris A. Phase II trial of pemetrexed (P) and bevacizumab (B) in patients (pts) with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC): an interim analysis. Journal of Clinical Oncology. 2007;25(supplement 18):p. 6049.
    1. Caponigro F, Formato R, Caraglia M, Normanno N, Iaffaioli RV. Monoclonal antibodies targeting epidermal growth factor receptor and vascular endothelial growth factor with a focus on head and neck tumors. Current Opinion in Oncology. 2005;17(3):212–217.
    1. Kyzas PA, Stefanou D, Batistatou A, Agnantis NJ. Potential autocrine function of vascular endothelial growth factor in head and neck cancer via vascular endothelial growth factor receptor-2. Modern Pathology. 2005;18(4):485–494.
    1. Whitehurst B, Flister MJ, Bagaitkar J, et al. Anti-VEGF-A therapy reduces lymphatic vessel density and expression of VEGFR-3 in an orthotopic breast tumor model. International Journal of Cancer. 2007;121(10):2181–2191.
    1. Kass ES, Greiner JW, Kantor JA, et al. Carcinoembryonic antigen as a target for specific antitumor immunotherapy of head and neck cancer. Cancer Research. 2002;62(17):5049–5057.
    1. Sharkey RM, Hajjar G, Yeldell D, et al. A phase I trial combining high-dose 90Y-labeled humanized anti-CEA monoclonal antibody with doxorubicin and peripheral blood stem cell rescue in advanced medullary thyroid cancer. Journal of Nuclear Medicine. 2005;46(4):620–633.
    1. Chatal J-F, Campion L, Kraeber-Bodéré F, et al. Survival improvement in patients with medullary thyroid carcinoma who undergo pretargeted anticarcinoembryonic-antigen radioimmunotherapy: a collaborative study with the French Endocrine Tumor Group. Journal of Clinical Oncology. 2006;24(11):1705–1711.
    1. Eura M, Chikamatsu K, Katsura F. A wild-type sequence p53 peptide presented by HLA-A24 induces cytotoxic T lymphocytes that recognize squamous cell carcinomas of the head and neck. Clinical Cancer Research. 2000;6(3):979–986.
    1. Hoffmann TK, Bier H, Donnenberg AD, Whiteside TL, De Leo AB. p53 as an immunotherapeutic target in head and neck cancer. Advances in Otorhinolaryngology. 2005;62:151–160.
    1. Ueda Y, Shimizu K, Itoh T. Induction of peptide-specific immune response in patients with primary malignant melanoma of the esophagus after immunotherapy using dendritic cells pulsed with MAGE peptides. Japanese Journal of Clinical Oncology. 2007;37(2):140–145.
    1. Vantomme V, Dantinne C, Amrani N, et al. Immunologic analysis of a phase I/II study of vaccination with MAGE-3 protein combined with the AS02B adjuvant in patients with MAGE-3-positive tumors. Journal of Immunotherapy. 2004;27(2):124–135.
    1. Zhu M, Marshall J, Cole D, Schlom J, Tsang KY. Specific cytolytic T-cell responses to human CEA from patients immunized with recombinant avipox-CEA vaccine. Clinical Cancer Research. 2000;6(1):24–33.
    1. Marshall JL, Gulley JL, Arlen PM, et al. Phase I study of sequential vaccinations with fowlpox-CEA(6D)-TRICOM alone and sequentially with vaccinia-CEA(6D)-TRICOM, with and without granulocyte-macrophage colony-stimulating factor, in patients with carcinoembryonic antigen-expressing carcinomas. Journal of Clinical Oncology. 2005;23(4):720–731.
    1. Lu Y, Zhang Z, Liu Q, et al. Immunological protection against HPV16 E7-expressing human esophageal cancer cell challenge by a novel HPV16-E6/E7 fusion protein based-vaccine in a Hu-PBL-SCID mouse model. Biological and Pharmaceutical Bulletin. 2007;30(1):150–156.

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