Delgado-Enciso I, Galván-Salazar HR, Coronel-Tene CG, Sánchez-Santillán CF, Enriquez-Maldonado IG, Rojas-Martínez A, Ortiz-López R, Baltazar-Rodriguez LM, Elizalde A, Silva-Platas CI

Idioma: Ingles.
Referencias bibliográficas: 29
Paginas: 101-106
Archivo PDF: 100.23 Kb.

RESUMEN

Los adenovirus (vectores adenovirales) usados en la terapia génica pueden eliminar a las células neoplásicas mediante una replicación selectiva y/o a través de la expresión de genes proapoptóticos, inmunogénicos o tóxicos. Sin embargo, un vector adenoviral puede provocar efectos anticancerosos aun en ausencia de replicación o de la expresión de un gen terapéutico. El presente estudio evalúa la eficacia terapéutica de los vectores adenovirales, por si solos (sin efecto por replicación o por un gen terapéutico), en neoplasias dependientes del papilomavirus humano (N-PVH). Los ensayos in vivo fueron realizados en dos modelos murinos (ratones) de N-PVH, un modelo fue inmunocompetente y otro inmunodeficiente. En ellos se comparó el efecto de la administración intratumoral de solución salina (PBS) con la administración de un vector adenoviral sin capacidad replicativa ni gen terapéutico (Ad-BGal). En ratones inmunocompetentes, la administración del vector adenoviral Ad-BGal redujo significativamente el crecimiento tumoral en comparación con PBS, en tanto que en ratones inmunodeficientes no se observaron diferencias. En conclusión, el presente trabajo apoya el uso de vectores adenovirales en el tratamiento de N-PVH, pues son capaces de generar un efecto antitumoral en individuos inmunocompetentes, aun en ausencia de gen terapéutico o replicación del vector viral.

REFERENCIAS (EN ESTE ARTÍCULO)

1. Donoso E, Cuello M, Villarroel del P L. Reducción de la mortalidad por cáncer cérvico uterino en chile, 1990-2003. Rev Chil Obstet Ginecol 2006; 71: 307-12.

2. Twombly RUS. girls to receive HPV vaccine but picture unclear on potential worldwide use, acceptance. J Natl Cancer Inst 2006; 98: 1030-2.

3. Rojas-Martínez A, Martínez-Dávila IA, Hernández-García A, Aguilar-Córdova E, Barrera-Saldaña HA. Genetic therapy of cancer. Rev Invest Clin 2002; 54: 57-67.

4. Cervantes-García D, Ortiz-López R, Mayek-Pérez N, Rojas- Martínez A. Oncolytic virotherapy. Annals of Hepatology 2008; 7: 34-45.

5. Bangari DS, Mittal SK. Current strategies and future directions for eluding adenoviral vector immunity. Curr Gene Ther 2006; 6: 215-26.

6. Hallden G, Hill R, Wang Y, et al. Novel immunocompetent murine tumor models for the assessment of replication-competent oncolytic adenovirus efficacy. Mol Ther 2003; 8: 412–24.

7. Hamada K, Sakaue M, Alemany R, et al. Adenovirus-mediated transfer of HPV 16 E6/E7 antisense RNA to human cervical cancer cells. Gynecol Oncol 1996; 63: 219-27.

8. Ahn WS, Bae SM, Lee KH, et al. Recombinant adenovirus-p53 gene transfer and cell-specific growth suppression of human cervical cancer cells in vitro and in vivo. Gynecol Oncol 2004; 92: 611-21.

9. Das S, El-Deiry WS, Somasundaram K. Efficient growth inhibition of HPV 16 E6-expressing cells by an adenovirus-expressing p53 homologue p73beta. Oncogene 2003; 22: 8394-402.

10. Kong W, Sun J, Lin C, et al. Experimental study on adenovirusmediated transfer of p53 or adenovirus- mediated transfer of p53 combined with radiotherapy for human cervical cancer cell line HeLa cells. Zhonghua Fu Chan Ke Za Zhi 2002; 37: 352-5.

11. Hamada K, Alemany R, Zhang WW, Hittelman WN, et al. Adenovirus- mediated transfer of a wild-type p53 gene and induction of apoptosis in cervical cancer. Cancer Res 1996; 56: 3047-54.

12. Tsao YP, Huang SJ, Chang JL, et al. Adenovirus-mediated p21 (WAF1/SDII/CIP1) gene transfer induces apoptosis of human cervical cancer cell lines. J Virol 1999; 73: 4983-90.

13. Green KL, Southgate TD, Mulryan K, et al. Diffusible VP22- E2 protein kills bystander cells and offers a route for cervical cancer gene therapy. Hum Gene Ther 2006; 17: 147-57.

14. Huh WK, Gomez-Navarro J, Arafat WO, Xiang J, et al. Bax-induced apoptosis as a novel gene therapy approach for carcinoma of the cervix. Gynecol Oncol 2001; 83: 370-7.

15. Ip SM, Huang TG, Yeung WS, Ngan HY. pRb-expressing adenovirus Ad5-Rb attenuates the p53-induced apoptosis in cervical cancer cell lines. Eur J Cancer 2001; 37: 2475-83.

16. Bilsland AE, Anderson CJ, Fletcher-Monaghan AJ, McGregor F, et al. Selective ablation of human cancer cells by telomerasespecific adenoviral suicide gene therapy vectors expressing bacterial nitroreductase. Oncogene 2003; 22: 370-80.

17. Wildner O, Morris JC, Vahanian NN, et al. Adenoviral vectors capable of replication improve the efficacy of HSVtk/GCV suicide gene therapy of cancer. Gene Ther 1999; 6: 57-62.

18. Ahn WS, Bae SM, Kim TY, et al. A therapy modality using recombinant IL-12 adenovirus plus E7 protein in a human papillomavirus 16 E6/E7-associated cervical cancer animal model. Hum Gene Ther 2003; 14: 1389-99.

19. Qin XQ, Tao N, Dergay A, et al. Interferon-beta gene therapy inhibits tumor formation and causes regression of established tumors in immune-deficient mice. Proc Natl Acad Sci U S A 1998; 95: 14411-16.

20. Gilligan MG, Knox P, Weedon S, et al. Adenoviral delivery of B7-1 (CD80) increases the immunogenicity of human ovarian and cervical carcinoma cells. Gene Ther 1998; 5: 965-74.

21. Delgado-Enciso I, Cervantes-García D, Martínez-Dávila IA, Ortiz-López R, Alemany-Bonastre R, Silva-Platas CI, et al. A potent replicative delta-24 adenoviral vector driven by the promoter of human papillomavirus 16 that is highly selective for associated neoplasms. J Gene Med 2007; 9: 852-61.

22. Jones N, Shenk T. An adenovirus type 5 early gene function regulates expression of other early viral genes. Proc Natl Acad Sci USA 1979; 76: 3665-9.

23. AdEasy Vector System. Application Manual, Versión 1.4. California, USA.

24. Jogler C, Hoffmann D, Theegarten D, et al. Replication properties of human adenovirus in vivo and in cultures of primary cells from different animal species. J Virol 2006; 80: 3549-58.

25. Di Paolo NC, Tuve S, Ni S, Hellstrom KE, et al. Effect of adenovirus-mediated heat shock protein expression and oncolysis in combination with low-dose cyclophosphamide treatment on antitumor immune responses. Cancer Res 2006; 66: 960-9.

26. Courreges MC, Benencia F, Conejo-Garcia JR, et al. Preparation of apoptotic tumor cells with replication-incompetent HSV augments the efficacy of dendritic cell vaccines. Cancer Gene Ther 2006; 13: 182-93.

27. Opalka B, Dickopp A, Kirch HC. Apoptotic genes in cancer therapy. Cells Tissues Organs 2002; 172: 126-32.

28. Cook JL, Routes JM. Adenovirus E1A gene-induced tumor cell rejection through cellular sensitization to immune and nonimmune apoptotic injuries. Front Biosci 2005; 10: 1396-414.

29. Phelps, W. C., Yee, C. L., Munger, K., Howley, P. M. Functional and sequence similarities between HPV16 E7 and adenovirus E1A. Curr Top Microbiol Immunol 1989; 144: 153-66.