Immune response in cervical cancer. Strategies for the development of therapeutic vaccines
Main Article Content
Keywords
Cervical cancer, Human papillomavirus, Immune response antigens, Vaccines
Abstract
High-risk human papillomaviruses (HR-HPV), as HPV-16, evade immune recognition through the inactivation of cells of the innate immune response. HPV-16 E6 and E7 genes down-regulate type I interferon response. They do not produce viremia or cell death; therefore, they do not cause inflammation or damage signal that alerts the immune system. Virus-like particles (VLPs), consisting of structural proteins (L1 and L2) of the main HR-HPV types that infect the genitourinary tract, are the most effective prophylactic vaccines against HR-HPV infection. While for the high grade neoplastic lesions, therapeutic vaccines based on viral vectors, peptides, DNA or complete HR-HPV E6 and E7 proteins as antigens, have had limited effectiveness. Chimeric virus-like particles (cVLPs) that carry immunogenic peptides derived from E6 and E7 viral proteins, capable to induce activation of specific cytotoxic T lymphocytes, emerge as an important alternative to provide prophylactic and therapeutic activity against HR-HPV infection and cervical cancer.
References
Forman D, de Martel C, Lacey Ch J, Soerjomataram I, Lortet-Tieulent J, Bruni, et al. Global Burden of Human Papillomavirus and Related Diseases. Vaccine. 2012;30S:F12-F23.
Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189:12-9.
Muñoz N, Bosch FX, de Sanjosé S, Herrero R, Castellsagué X, Shah KV, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. International Agency for Research on Cancer Multicenter Cervical Cancer Study Group. N Engl J Med. 2003;348(6):518-27.
Laimins LA. Regulation of transcription and replication by human papillomaviruses. En: McCance DJ, editor. Human Tumor Viruses. Washington, USA: American Society for Microbiology; 1998. p. 201-222.
Chen XS, Garcea RL, Goldberg I, Casini G, Harrison SC. Structure of small virus-like particles assembled from the L1 protein of human papillomavirus 16. Mol Cell. 2000;5(3):557-67.
Doorbar J, Quint W, Banks L, Bravo IG, Stoler M, Broker TR, et al. The Biology and Life-Cycle of Human Papillomaviruses. Vaccine. 2012;30S:F55-F70.
Stanley MA. Epithelial Cell Responses to Infection with Human Papillomavirus. Clin Microbiol Rev. 2012;25(2):215-22.
Kanodia S, Fahey LM, Kast WM. Mechanisms used by human papillomaviruses to escape the host immune response. Curr Cancer Drug Targets. 2007;7:79-89.
Park JS, Kim EJ, Kwon HJ, Hwang ES, Namkoong SE, Um SJ. Inactivation of interferon regulatory factor-1 tumor suppressor protein by HPV E7 oncoprotein. Implication for the E7-mediated immune evasion mechanism in cervical carcinogenesis. J Biol Chem. 2000;275(10):6764-9.
Moscicki AB, Schiffman M, Burchell A, Albero G, Giuliano AR, Goodman MT, et al. Updating the Natural History of Human Papillomavirus and Anogenital Cancers. Vaccine. 2012;30S:F24-F33.
De Jong A, van der Burg SH, Kwappenberg KM, van der Hulst JM, Franken KL, Geluk A, et al. Frequent detection of human papillomavirus 16 E2-specific T-helper immunity in healthy subjects. Cancer Res. 2002;62:472-9.
Welters MJ, de Jong A, van den Eeden SJ, van der Hulst JM, Kwappenberg KM, Hassane S, et al. Frequent display of human papillomavirus type 16 E6-specific memory T-helper cells in the healthy population as witness of previous viral encounter. Cancer Res. 2003;63(3):636-41.
Woo Y, Sterling J, Damay I, Coleman N, Crawford R, van der Burg SH, et al. Characterising the local immune responses in cervical intraepithelial neoplasia: a cross-sectional and longitudinal analysis. BJOG. 2008;115:1616-22.
Carter JJ, Koutsky LA, Hughes JP, Lee SK, Kuypers J, Kiviat N, Galloway DA. Comparison of human papillomavirus types 16,18, and 6 capsid antibody responses following incident infection. J Infect Dis. 2000;181:1911-9.
Carter JJ, Madeleine MM, Shera K, Schwartz SM, Cushing-Haugen KL, Wipf GC, et al. Human papillomavirus 16 and 18 L1 serology compared across anogenital cancer sites. Cancer Res. 2001;61:1934-40.
Ochmus-Kudielka I, Schneider A, Braun R, Kimmig R, Koldovsky U, Schneweis KE, et al. Antibodies against the human papillomavirus type 16 early proteins in human sera: correlation of anti-E7 reactivity with cervical cancer. J Natl Cancer Inst. 1989;81:1698-704.
Moody CA, Laimins LA. Human papillomavirus oncoproteins: pathways to transformation. Nat Rev Cancer. 2010;10:550-60.
Kobayashi A, Weinberg V, Darragh T, Smith-McCune K. Evolving immunosuppressive microenvironment during human cervical carcinogenesis. Mucosal Immunol. 2008;1:412-20.
Zhou J, Sun XY, Stenzel DJ, Frazer IH. Expression of vaccinia recombinant HPV 16 L1 and L2 ORF proteins in epithelial cells is sufficient for assembly of HPV virion-like particles. Virology. 1991;185(1):251-7.
Schiller JT, Castellsagué X, Garland SM. A Review of Clinical Trials of Human Papillomavirus Prophylactic Vaccines. Vaccine. 2012;30S:F123-F138.
Jagu S, Kwak K, Karanam B, Huh WK, Damotharan V, Chivukula SV, et al. Optimization of multimeric human papillomavirus L2 vaccines. PLoS One. 2013;8(1):1-8.
Stanley M, Pinto LA, Trimble C. Human Papillomavirus Vaccines – Immune Responses. Vaccine. 2012;30S:F83-F87.
Cid-Arregui A. Therapeutic vaccines against human papillomavirus and cervical cancer. Open Virol. 2009;3:67-83.
Gissmann L, Nieto K. The Therapeutic Vaccine: Is it Feasible? Arch Med Res. 2009;40:493-8.
Ma B, Maraj B, Tran NP, Knoff J, Chen A, Alvarez RD, et al. Emerging human papillomavirus vaccines. Expert Opin Emerg Drugs. 2012;17(4):469-92.
Kaufmann AM, Nieland JD, Jochmus I, Baur S, Friese K, Gabelsberger J, et al. Vaccination trial with HPV16 L1E7 chimeric virus-like particles in women suffering from high grade cervical intraepithelial neoplasia (CIN 2/3). Int J Cancer. 2007;121:2794-800.
Gómez Lim MA. Transgenic plants in therapeutically valuable protein production. Transgenic Plant J. 2007;1:256-66.
Paz de la Rosa G, Monroy-García A, Mora-García MD, Reynaga-Peña CG, Hernandez-Montes J, Weiss-Steider B, et al. An HPV 16 L1-based chimeric human papilloma virus-like particles containing a string of epitopes produced in plants is able to elicit humoral and cytotoxic T-cell activity in mice. Virol J. 2009;6:2.
Monroy-García A, Gómez-Lim MA, Weiss-Steider B, Hernández-Montes J, Huerta-Yepez S, Rangel-Santiago JF, et al. Immunization with an HPV-16 L1 based chimeric virus-like particle containing HPV-16 E6 and E7 epitopes elicits long-lasting prophylactic and therapeutic efficacy in an HPV-16 tumor mice model. Arch Virol. 2014;59:291:305.