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2005, Número 1

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Cir Cir 2005; 73 (1)


Vacunas preventivas y ensayos clínicos de inmunoterapia contra cáncer cervicouterino

Valdespino-Gómez VM

Idioma: Español
Referencias bibliográficas: 70
Paginas: 57-69
Archivo PDF: 114.11 Kb.


RESUMEN

El cáncer cervicouterino (CaCu) invasor se mantiene como un gran problema de salud pública en las mujeres de todo el mundo. Para mejorar el control de la enfermedad se requieren nuevas estrategias terapéuticas adyuvantes. Los avances en inmunología, genómica y proteómica han permitido entender las bases celulares y moleculares de muchos cánceres. El CaCu es uno de los modelos tumorales biológicos cuya iniciación y promoción se relacionan con la infección persistente por virus del papiloma humano (VPH) oncogénicos. Durante la infección viral y el desarrollo de lesiones preinvasoras o invasoras asociadas, los VPH coexpresan proteínas estructurales y no estructurales. Estas proteínas “tempranas” o “tardías” son el blanco antigénico de la respuesta inmune. Los ensayos para estimular la respuesta inmune humoral o celular anti-VPH son el objetivo de la inmunoprevención y de la inmunoterapia contra el CaCu. Recientemente en un ensayo clínico controlado tipo III de vacunación profiláctica contra la infección cervical por VPH 16, en el que se emplearon partículas semejantes a virus de la proteína de la cápside L1, se demostró protección contra la infección específica y contra las lesiones precancerosas asociadas. Aunque los resultados preliminares de los ensayos clínicos de inmunoterapia contra CaCu no han provocado efecto clínico, ocasionalmente han demostrado incremento en la respuesta de los linfocitos contra los VPH. En un ensayo reciente con células dendríticas pulsadas con la oncoproteína E7 de VPH 18 como adyuvante, hubo remisión temporal de la enfermedad y mejoramiento de la calidad de vida en una paciente con CaCu metastásico. Nuevos y diferentes ensayos clínicos de vacunación profiláctica contra la infección por VPH están siendo aplicados, lo cual es esperanzador. El éxito en los ensayos clínicos de inmunoterapia anti-VPH en pacientes con CaCu está menos cercano. En el presente artículo se revisan las bases científicas del desarrollo de las vacunas profilácticas y terapéuticas contra la infección persistente por VPH y contra las lesiones cervicales preinvasoras e invasoras asociadas, así como los principales resultados de los ensayos clínicos de vacunación profiláctica y de inmunomo- dulación terapéutica en CaCu.


REFERENCIAS (EN ESTE ARTÍCULO)

  1. Bosch FX, de Sanjose S. Human papillomavirus and cervical cancer-burden and assessment of causality. J Natl Cancer Inst Monogr 2003;31:3-13.

  2. 2. Nabel GJ. Genetic, cellular and immune approaches to disease therapy: past and future. Nat Med 2004;10:135-141.

  3. 3. zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer 2002;2:342-350

  4. 4. Schiffman M, Kruger KS. Natural history of anogenital human papillomavirus infection and neoplasia. J Natl Cancer Inst Monogr 2003;31:14-19.

  5. 5. DeVita V, Hellman S, Rosenberg S, Cancer. Principles & practice of oncology. 6th edition. Philadelphia: Lippincott Williams & Wilkins; 2001. pp. 1522-1548.

  6. 6. Eiben GL, Velders MP, Kast WN. The cell-mediated immune response to human papillomavirus-induced cervical cancer: implications for immunotherapy. Adv Cancer Res 2002:113-148

  7. 7. Scott M, Nakagawa M, Moscicki AB. Cell-mediated immune response to human papillomavirus infection. Clin Diagn Lab Immunol 2001;8:209-220.

  8. 8. Tindle RW. Immune evasion in human papillomavirus-associated cervical cancer. Nat Rev Cancer 2002;2:59-65.

  9. 9. Frazer IH. Prevention of cervical cancer through papillomavirus vaccination. Nat Rev Immunol 2004;4:46-54.

  10. 10. Nonn M, Schinz M, Zumbach K, et al. Dendritic cell-based tumor vaccine for cervical cancer. I. In vitro stimulation with recombinant protein-pulsed dendritic cells induce specific T cells to HPV16 E7 or HPV18 E7. J Cancer Res Clin Oncol 2003;129:511-520.

  11. 11. Rohan ET, Burk RD, Franco EL. Toward a reduction of the global burden of cervical cancer. Am J Obstet Gynecol 2003;189:S37-S39.

  12. 12. Wang SS, Hildesheim A. Viral and host factors in human papillomavirus persistence and progression. J Natl Cancer Inst Monogr 2003;31:35-40.

  13. 13. Berumen J, Ordoñez RM, Salmeron J, et al. Asian-American variants of human papillomavirus 16 and risk for cervical cancer: a case control study. J Natl Cancer Inst 2001;93:1325-1330.

  14. 14. Sherman ME, Schiffman M, Cox JT. Effects of age and HPV viral load on colposcopy triage: data from the randomized atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion traiage study (ALTS). J Natl Cancer Inst 2002; 94:102-107.

  15. 15. Lazo PA. The molecular genetics of cervical carcinoma. Br J Cancer 1999;80:2008-2018.

  16. 16. Hanahan D, Winberg R. The hallmarks of cancer. Cell 2000;100:57-70.

  17. 17. Giuliano A. Cervical carcinogenesis: the role of co-factors and generation of reactive oxygen species. Salud Publica Mex 2003;45:S354-S354.

  18. 18. Pinto AP, Tulio S, Cruz OR. HPV cofactors in cervical carcinogenesis. Rev Assoc Med Bras 2002;48:73-78.

  19. 19. Ho GY, Bierman R, Beardsley L, et al. Natural history of cervico-vaginal papillomavirus in young women. N Engl J Med 1998;338: 423-428.

  20. 20. Hildesheim A, Wang SS. Host and viral genetics and risk of cervical cancer: a review. Virus Res 2002;89:229-240.

  21. 21. Petry KU, Sheffel D, Bode U, et al. Cellular immunodeficiency enhances the progression of human papillomavirus-associated cervical lesions. Int J Cancer 1994;57:836-840.

  22. 22. Rocha ZL, Barrios T, Garcia CA, et al. Cervical secretory immunoglobulin A to humman papillomavirus type 16 (HPV 16) from HVP 16-infected women inhibit HPV 16 virus-like particle-induced hemagglutination of mouse red blood cells. FEMS Immun Med Microb 2001;31:47-51.

  23. 23. Valdespino GV, Rocha ZL. Inmunoterapia mediada por linfocitos T en pacientes con cáncer. Cir Ciruj 2003;71:235-244.

  24. 24. Chen LP, Thomas EK, Hu SL, Hellstrom I, Hellstrom KE. Human papillomavirus type 16 nucleoprotein E7 is a tumor rejection antigen. Proc Natl Acad Sci USA 1991;8:110-114.

  25. 25. Feltkamp MC, Smits HL, Vierboom MP, et al. Vaccination with cytotoxic T lymphocyte epitope-containing peptide protects against a tumor induced by human papillomavirus tyepe 16-transformed cells. Eur J Immunol 1993;23:2242-2249.

  26. 26. De Bruijn ML, Schuurhuis DH, Vierboom MP, et al. Immunization with human papillomavirus type 16 (HPV16) oncoproteins loaded dendritic cells as well as protein in adjuvant MHC clas I restricted protection to HPV-induced tumor cells. Cancer Res 1998 58:724-731.

  27. 27. Eiben GL, Velders MP, Schreiber H, et al. Establisment of an HLA-A*0201 human papillomavirus type 16 tumor model to determine the efficacy of vaccination strategies in HLA-A*0201 transgenic mice. Cancer Res 2002;62:5792-5799.

  28. 28. Villa LL. Vaccines against papillomavirus infections and disease. Salud Pub Mex 2003;45:S443-S448.

  29. 29. Konya J, Dillner J. Immunity to oncogenic human papillomavirus. Adv Cancer Res 2001;82:205-238.

  30. 30. Flint SJ, Enquist LW, Racaniello VR. Skalka AM. Principles of Virolo-gy. Molecular biology, pathogenesis, and control of animal viruses. 2nd edition: Washington, DC: ASM Press; 2004. pp. 530-595,554-700.

  31. 31. Nees M, Geoghegan JM, HymanT, Frank S, Miller L, Woodworth CD. Papillomavirus type 16 oncogenes downregulate expression of interferon-response genes and upregulate proliferation-associated and NF-êB response genes in cervical keratinocytes. J Virol 2001;75: 4283-4296.

  32. 32. Matthews K, Leong CM, Baxter L, et al. Depletion of Langerhans cells in human papillomavirus type 16-infected skin is associated with E6-mediated downregulation of E-cadherin. J Virol 2003;77:8378-8385.

  33. 33. Kono K, Ressing ME, Brandt MR. Decreased expression of signal-transducing zeta chain in peripheral T cells and natural killer cells in patients with cervical cancer. Clin Cancer Res 1996;2:1825-1828.

  34. 34. Ressing ME, Sette A, Brandt RMP, et al. Human CTL epitopes encoded by human papillomavirus type 16 E6 and E7 identified through in vivo and in vitro immunogenicity studies of HLA-A*0201-binding peptides. J Immunol 1995;154:5934-5943.

  35. 35. Parmiani G, Castelli C, Anichini A, et al. Cancer immunotherapy with peptide-based vaccines: what have we achieved? Where are we going? J Natl Cancer Inst 2002;94:805-818.

  36. 36. Lowy RD, Frazer HI. Prophylactic human papillomavirus vaccines. J Natl Cancer Inst Monogr 2003;31:111-116.

  37. 37. Billich A. HPV vaccine. MedImmune/GlaxoSmithKline. Curr Opin Invest Drugs 2003;4:210-213.

  38. 38. Koutsky LA, Ault KA, Wheeler CM, et al. A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med 2002;347:1645-1651.

  39. 39. Hopfl R. Heim K, Christensen N, et al. Spontaneous regression of CIN and delayed-type hypersensitivity to HPV-16 oncoprotein E7. Lancet 2000;356:1985-1986.

  40. 40. Kols A, Sherrris J. HPV vaccines: promise and challenges. Pathology 2000:1-35.

  41. 41. Chen XJS, Garcea RL, Goldberg I, et al. Structure of small virus-like particles assembled from L1 protein of human papillomavirus 16. Mol Cell Biol 2000;5:557-567.

  42. 42. Tobery TW, Smith JF, Kuklin N, et al. Effect of vaccine delivery system on the inducton of HPV 16L1-specific humoral and cell-mediated immune response in immunized Rhesus macaques. Vaccine 2003;21:1539-1547.

  43. 43. Nardelli-Haeflinger D, Wirthner D, Schiller JT, et al. Specific antibody levels at the cervix during the menstrual cycle of women with human papillomavirus 16 virus-like particles. J Natl Cancer Inst 2003;95:1128-1137.

  44. 44. Pinto LA, Edwards J, Castle PE, et al. Cellular immune responses to human papillomavirus (HPV)-16 in healthy volunteers immunized with recombinant HPV-16 L1 virus-like particles. J Infect Dis 2003;188:327-338.

  45. 45. Crum CP. The beginning of the end for cervical cancer? N Engl J Med 2002;347:1703-1705.

  46. 46. Zwaveling S, Ferreira MSC, Nouta J, et al. Established human papillomavirus type 16-expresing tumors a effectively erradicated following vaccination with long peptides. J Immunol 2002;69:350-358.

  47. 47. Gao FG, Khammanivong V, Liu WJ, Legatt GR, Frazer IH, Fernando GJ. Antigen-specific CD4+T-cell is required to activate memory CD8+ T cell to a fully functional tumor killer cell. Cancer Res 2002;62:6438-6441.

  48. 48. Marzo AL, Kinner BF, Lake R, et al. Tumor-specific CD4+ T cells have a major “post-licensing” role in CTL mediated anti-tumor immunity. J Immunol 2000:6047-6055.

  49. 49. Kaufmann AM, Nieland J, Schinz M, et al. HPV 16 L1 E7 chimeric virus-like particles induce specific HLA-restricted T cells in humans after in vitro vaccination. Int J Cancer 2001;92:285-293.

  50. 50. Da Silva DM, Schiller JT, Kast WM. Heterologous boosting increases immunogenicity of chimeric papillomavirus virus-like particles vaccines. Vaccine 2003;21:3219-3227.

  51. 51. Borysiewicz LK, Fiander A, Nimako M, et al. A recombinant vaccinia virus encoding human papillomavirus types 16 and 18, E6 and E7 proteins as immunotherapy for cervical cancer. Lancet 1996, 347:1523-1527.

  52. 52. Adams M, Borysiewicz L, Fiander A, et al. Clinical studies of human papilloma vaccines in pre-invasive and invasive cancer. Vaccine 2001;19:2549-2556.

  53. 53. Steller MA, Gurski KJ, Murakami M, Daniel RW, Shah KV, Celis E, Sette A, Trimble EL, Park RC, Marincola FM. Cell-mediated immunologic responses in cervical and vaginal cancer patients immunized with lipidated epitope of human papillomavirus type 16 E7. Clin Cancer Res 1998;4:2103-2109.

  54. 54. Tsuda N, Mochizuki K, Harada M, et al. Vaccination with predesignat-ed or evidence-based peptides for patientes with recurrent gynecologic cancer. J Immunother 2004;27:60-72.

  55. 55. Ferrara A, Nonn M, Sehr P, et al. Dendritic cell-based tumor vaccines for cervical cancer. II. Results of a clinical pilot study in 15 individual patients. J Cancer Res Clin Oncol 2003;129:521-530.

  56. 56. Santin AD, Bellone S, Gokden M, Cannon MJ, Parham GP. Vaccination with HPV-18. E7-pulsed dendritic cells in a patient with metastatic cervical cancer. N Engl J Med 2002;346:1752-1753.

  57. 57. Muderspach L, Wilczynski S, Roman L, et al. A phase I trial of a human papillomavirus (HPV) peptide vaccine for women with high grade cervical and vulvar intraepithelial neoplasia who are HPV 16 positive. Clin Cancer Res 2000;6:3406-3416.

  58. 58. Baldwin P, van der Burg SH, Boswell CM, et al. Vaccinia-expressed human papillomavirus 16 and 18 E6 and E7 as a therapeutic vaccination for vulval and vaginal intraepithelial neoplasia. Clin Cancer Res 2003;9:5205-5213

  59. 59. Kaufmann AM, Stern PL, Rankin EM, et al. Safety and immunogenicity of TA-HPV, a recombinant vaccinia virus expressing modified human papillomavirus (HPV)-16 and HPV-18 E6 and E7 genes in women with progressive cervical cancer. Clin Cancer Res 2002;8: 3676-3685.

  60. 60. Santin AD, Hermonat PL, Ravaggi A, et al. Induction of human papillomavirus-specific CD4+ and CD8+ lymphocytes by E7-pulsed autologous dendritic cells in patients with human papillomavirus type 16- and -18-positive cervical cancer. J Virol 1999;73:5402-5410.

  61. 61. Ribas A, Butterfield LH, Glaspy JA, Economou JS. Cancer immunotherapy using gene-modified dendritic cells. Curr Gen Ther 2002;2: 57-78.

  62. 62. Salio M, Shepher D, Dunbar PR, et al. Mature dendritic cells prime functionally superior melan-a-specific CD8+ lymphocytes as compar-ed with nonprofessional APC. J Immunol 2001;167:1188-1197.

  63. 63. Goldie SJ, Kuhn L, Denny L, et al. Policy analysis of cervical cancer screening strategies in low-resource settings: clinical benefits and cost-effectiveness. JAMA 2001; 285:3010-3015 (erratum 286:1026).

  64. 64. Monz M, Ling M, Hung CF, Wu TC. HPV DNA vaccines. Front Biosci 2003;8:d55-68.

  65. 65. Garcia CA. Vaccines against human papillomavirus and perspectives for the prevention and control of cervical cancer. Salud Publica Mex 2003;45:S437-S442.

  66. 66. Schultze JL, Vonderheide RH. From cancer genomics to cancer immunotherapy: toward second-generation tumor antigens. Trends Immunol 2001;22,9:516-523.

  67. 67. Monzavi KB. Keiber ET. Current concepts in cancer vaccine strategies. Biotechniques 2001;30:170-189.

  68. 68. Kather A, Ferrara A, Nonn M, et al. Identification of a naturally processed HLA-A*0201 HPV18 T cell epitope by tumor cell mediated in vitro vaccination. Int J Cancer 2003;104:345-353.

  69. 69. Lamikanra A, Pan ZK, Issacs SN, Wu TC. Paterson Y. Regression of established human papillomavirus type 16 (HPV-16) immortalized tumors in vitro by vaccinia viruses expressing different forms of HPV-16 E7 correlates with enhanced CD8(+) T-cell responses that home to the tumor site. J Virol 2001;75:9654-9664.

  70. 70. Kim TY, Myoung HJ, Kim JH, et al. Both E7 and CpG-oligodeoxynucleotide are required for protective immunity against challenge with human papillomavirus 16 (E6/E7) immortalized tumor cells: involvement of CD4+ and CD8+ T cells in protection. Cancer Res 2002;62:7234-7240.




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