2,424
Views
4
CrossRef citations to date
0
Altmetric
Original Research

A therapeutic DNA vaccine and gemcitabine act synergistically to eradicate HPV-associated tumors in a preclinical model

, , , , , , , , , , & show all
Article: 1949896 | Received 30 Apr 2021, Accepted 24 Jun 2021, Published online: 25 Jul 2021

References

  • De MC, Georges D, Bray F, Ferlay J, Clifford GM. Articles Global burden of cancer attributable to infections in 2018 : a worldwide incidence analysis. Lancet Glob Heal. 2020;8(2):e180–13. doi:10.1016/S2214-109X(19)30488-7.
  • Wardak S. Human Papillomavirus (HPV) and cervical cancer. Med Dosw Mikrobiol. 2016;68:73–84.
  • Siegel RL, Miller KD. Cancer Statistics, 2020. CA Cancer J Clin. 2020;70(1):7–30. doi:10.3322/caac.21590.
  • WHO report on cancer: setting priorities, investing wisely and providing care for all. WHO-CancerReport-2020-Global Profile. Geneva:World Health Organization; 2020.
  • Survival rates for cervical cancer. American Cancer Society. 2020. Web page (https://www.cancer.org/cancer/cervical-cancer/detection-diagnosis-staging/survival/en/, accessed January 2021).
  • Tseng J, Yen M, Twu N, Lai C, Horng H. Prognostic nomogram for overall survival in stage IIB-IVA cervical cancer patients treated with concurrent chemoradiotherapy. YMOB. 2010;202(2):174.e1–174.e7. doi:10.1016/j.ajog.2009.09.028.
  • Gadducci A, Tana R, Cosio S, Cionini L. Treatment options in recurrent cervical cancer (Review). Oncol Lett. 2010:3–11. doi:10.3892/ol.
  • Bracci L, Schiavoni G, Sistigu A, Belardelli F. Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer. Cell Death Differ. 2014;21(1):15–25. doi:10.1038/cdd.2013.67.
  • Carmichael J. The role of gemcitabine in the treatment of other tumours. British Journal of Cancer. 1998;78(S3):21–25. doi:10.1038/bjc.1998.750.
  • Mini E, Nobili S, Caciagli B, Landini I, Mazzei T. symposium article Cellular pharmacology of gemcitabine. Gemcitabine Ten Years Clin Exp. Sept 2005;19–21. doi:10.1093/annonc/mdj941. Monast. di Treviso, Italy. 2006;17\(Supplement 5):v7–v12.
  • Amrutkar M, Gladhaug IP. Pancreatic cancer chemoresistance to gemcitabine. Cancers (Basel). 2017;9:157. doi:10.3390/cancers9110157.
  • De Sousa Cavalcante L, Gemcitabine MG. Metabolism and molecular mechanisms of action, sensitivity and chemoresistance in pancreatic cancer. Eur J Pharmacol. 2014;741:8–16. doi:10.1016/j.ejphar.2014.07.041.
  • Sakamoto H, Kitano M, Suetomi Y, Takeyama Y, Ohyanagi H, Nakai T, Yasuda C, Kudo M. Comparison of standard-dose and low-dose gemcitabine regimens in pancreatic adenocarcinoma patients: a prospective randomized trial. J Gastroenterol. 2006;41:70–76. doi:10.1007/s00535-005-1724-7.
  • Alexopoulos A, Karamouzis MV, Rigatos G. In vivo synergism between docetaxel and gemcitabine in patients with metastatic breast cancer: general concepts and future perspectives. Semin Oncol. 2004;31(2 SUPPL. 5):25–30. doi:10.1053/j.seminoncol.2004.03.024.
  • Hirooka Y, Kawashima H, Ohno E, Ishikawa T, Kamigaki T, Goto S, Takahara M, Goto H. Comprehensive immunotherapy combined with intratumoral injection of zoledronate-pulsed dendritic cells, intravenous adoptive activated T lymphocyte and gemcitabine in unresectable locally advanced pancreatic carcinoma: a phase I/II trial. Oncotarget. 2018;9(2):2838–2847. doi:10.18632/oncotarget.22974.
  • Hirooka Y, Itoh A, Kawashima H, Hara K, Nonogaki K, Kasugai T, Ohno E, Ishikawa T, Matsubara H, Ishigami M, et al. A combination therapy of gemcitabine with immunotherapy for patients with inoperable locally advanced pancreatic cancer. Pancreas 2009;38:3. doi:10.1097/MPA.0b013e318197a9e3.
  • Liu WM, Fowler DW, Smith P, Dalgleish AG. Pre-treatment with chemotherapy can enhance the antigenicity and immunogenicity of tumours by promoting adaptive immune responses. Br J Cancer. 2010;102:115–123. doi:10.1038/sj.bjc.6605465.
  • Suzuki E, Kapoor V, Jassar AS, Kaiser LR, Albelda SM. Gemcitabine selectively eliminates splenic Gr-1+/CD11b+ Myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity. Clin Cancer Res. 2005;11(18):6713–6721. doi:10.1158/1078-0432.CCR-05-0883.
  • Eriksson E, Wenthe J, Irenaeus S, Loskog A, Ullenhag G. Gemcitabine reduces MDSCs, tregs and TGFβ-1 while restoring the teff/treg ratio in patients with pancreatic cancer. J Transl Med. 2016;14(1):1–12. doi:10.1186/s12967-016-1037-z.
  • Rébé C, Végran F, Berger H, Ghiringhelli F. STAT3 activation. JAK-STAT. 2013;2(1):e23010. doi:10.4161/jkst.23010.
  • Diniz MO, Lasaro MO, Ertl HC, Ferreira LCS. Immune responses and therapeutic antitumor effects of an experimental DNA vaccine encoding human papillomavirus type 16 oncoproteins genetically fused to herpesvirus glycoprotein D. Clin Vaccine Immunol. 2010;17(10):1576–1583. doi:10.1128/CVI.00264-10.
  • Diniz MO, Cariri FAMO, Aps LRMM, Ferreira LCS. Enhanced therapeutic effects conferred by an experimental DNA vaccine targeting human papillomavirus-induced tumors. Hum Gene Ther. 2013;24(10):861–870. doi:10.1089/hum.2013.102.
  • Silva JR, Sales NS, Silva MO, Aps LRMM, Moreno ACR, Rodrigues EG, Ferreira LCS, Diniz MO. Expression of a soluble IL-10 receptor enhances the therapeutic effects of a papillomavirus-associated antitumor vaccine in a murine model. Cancer Immunol Immunother. 2019;68(5):753–763. doi:10.1007/s00262-018-02297-2.
  • Sales NS, Silva JR, Aps LRMM, Silva MO, Porchia BFMM, Ferreira LCS, Diniz MO. In vivo electroporation enhances vaccine-mediated therapeutic control of human papilloma virus-associated tumors by the activation of multifunctional and effector memory CD8 + T cells. Vaccine. 2017;(52)7240–7249. doi:10.1016/j.vaccine.2017.11.011.
  • Lin KY, Guarnieri FG, Staveley-O’Carroll KF, Levitsky HI, August JT, Pardoll DM, Wu TC. Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigen. Cancer Res. 1996;56:21–26.
  • Lasaro MO, Diniz MO, Reyes-Sandoval A, Ertl HC, Ferreira LCS. Anti-tumor DNA vaccines based on the expression of human papillomavirus-16 E6/E7 oncoproteins genetically fused with the glycoprotein D from herpes simplex virus-1. Microbes Infect. 2005;7(15):1541–1550. doi:10.1016/j.micinf.2005.05.024.
  • Diniz MO, Ferreira LCS. Enhanced anti-tumor effect of a gene gun-delivered DNA vaccine encoding the human papillomavirus type 16 oncoproteins genetically fused to the herpes simplex virus glycoprotein D. Brazilian J Med Biol Res. 2011;44(5):421–427. = Rev. Bras. Pesqui. médicas e biológicas/Soc. Bras. Biofísica … [et al.].
  • Candelaria M, Cetina L, De La Garza J, Dueñas-Gonzálz A. Clinical implications of gemcitabine in the treatment of cervical cancer. Eur J Cancer. 2007;5(1):37–43. doi:10.1016/S1359-6349(07)70014-9.
  • Mutch DG, Bloss JD. Gemcitabine in cervical cancer. Gynecol Oncol. 2003;90(2): Pt 2. doi:10.1016/S0090-8258(03)00338-X.
  • Jia Y, Xie J. Promising molecular mechanisms responsible for gemcitabine resistance in cancer. Genes Dis. 2015;2(4):299–306. doi:10.1016/j.gendis.2015.07.003.
  • Principe DR, Narbutis M, Kumar S, Park A, Viswakarma N, Dorman MJ, Kamath SD, Grippo PJ, Fishel ML, Hwang RF, et al. Long-Term gemcitabine treatment reshapes the pancreatic tumor microenvironment and sensitizes murine carcinoma to combination immunotherapy. Cancer Res. 2020;80(15):3101–3115. doi:10.1158/0008-5472.CAN-19-2959.
  • Zhang X, Wang D, Li Z, Jiao D, Jin L, Cong J, Zheng X, Low-Dose Gemcitabine XL. Treatment enhances immunogenicity and natural killer cell-driven tumor immunity in lung cancer. Front Immunol. 2020;11:331. doi:10.3389/fimmu.2020.00331.
  • Komdeur FL, Prins TM, Van De Wall S, Plat A, Wisman GBA, Hollema H, Daemen T, Church DN, de Bruyn M, Nijman HW. CD103+ tumor-infiltrating lymphocytes are tumor-reactive intraepithelial CD8+ T cells associated with prognostic benefit and therapy response in cervical cancer. Oncoimmunology 2017;6:9. doi:10.1080/2162402X.2017.1338230.
  • Stevanovi´c SS, Draper LM, Langhan MM, Campbell TE, Kwong ML, Wunderlich JR, Dudley ME, Yang JC, Sherry RM, Kammula US, et al. Complete regression of metastatic cervical cancer after treatment with human papillomavirus-targeted tumor-infiltrating T cells. J Clin Oncol. 2015. 10.1200/JCO.2014.58.9093.
  • Reiniš M. Genetically modified tumour vaccines producing IL-12 augment chemotherapy of HPV16-associated tumours with gemcitabine. Oncol Rep. 2011. doi:10.3892/or.2011.1221. Mar 18.
  • Chang L-S, Yan W-L, Chang Y-W, Yeh Y-C, Chen H-W, Leng C-H, Liu S-J. Gemcitabine enhances antitumor efficacy of recombinant lipoimmunogen-based immunotherapy. OncoImmunology. 2016;5(3):e1095433. doi:10.1080/2162402X.2015.1095433.
  • Jang HY, Han BS, Kwon B, Sin JI. Optimized gemcitabine therapy in combination with E7 peptide immunization elicits tumor cure by preventing ag-specific CTL inhibition in animals with large established tumors. DNA Cell Biol. 2018;37(10):850–860. doi:10.1089/dna.2018.4319.
  • Porchia BFMM, Moreno ACR, Ramos RN, Diniz MO, Lhtm DA, Rosa DS, Barbuto JAM, Boscardin SB, Ferreira LCS. Herpes simplex virus glycoprotein D targets a specific dendritic cell subset and improves the performance of vaccines to human papillomavirus-associated tumors. Mol Cancer Ther. 2017;16(9):1922–1933. doi:10.1158/1535-7163.MCT-17-0071.
  • Wu L, Liu H, Guo H, Wu Q, Yu S, Qin Y, Wang G, Wu Q, Zhang R, Wang L, et al. Circulating and tumor-infiltrating myeloid-derived suppressor cells in cervical carcinoma patients. Oncol Lett. 2018;15(6):9507–9515. doi:10.3892/ol.2018.8532.
  • Sevko A, Umansky V. Myeloid-derived suppressor cells interact with tumors in terms of myelopoiesis, tumorigenesis and immunosuppression: Thick as thieves. J. Cancer. 2013;4(1):3–11. doi:10.7150/jca.5047
  • Nowak AK, Robinson BWS, Lake RA. Gemcitabine exerts a selective effect on the humoral immune response : implications for combination chemo-immunotherapy. Cancer Res. 2002;62(8):2353–2358.
  • Le HK, Graham L, Cha E, Morales JK, Manjili MH, Bear HD. Gemcitabine directly inhibits myeloid derived suppressor cells in BALB/c mice bearing 4T1 mammary carcinoma and augments expansion of T cells from tumor-bearing mice. Int Immunopharmacol. 2009;9(7–8):900–909. doi:10.1016/j.intimp.2009.03.015.
  • Diniz MO, Sales NS, Silva JR, Ferreira LCS. Protection against HPV-16-associated tumors requires the activation of CD8+ effector memory t cells and the control of myeloid-derived suppressor cells. Mol Cancer Ther. 2016;15(8):1920–1930. doi:10.1158/1535-7163.MCT-15-0742.
  • Moreno ACR, Porchia BFMM, Pagni RL, Souza PDC, Pegoraro R, Rodrigues KB, Barros TB, Aps LRDMM, de Araújo EF, Calich VLG, et al. The combined use of melatonin and an indoleamine 2,3-dioxygenase-1 inhibitor enhances vaccine-induced protective cellular immunity to hpv16-associated tumors. Front Immunol. 2018 August;9:1914. doi:10.3389/fimmu.2018.01914.
  • Pei Q, Pan J, Zhu H, Ding X, Liu W, Lv Y, Zou X, Luo H. Gemcitabine-treated pancreatic cancer cell medium induces the specific CTL antitumor activity by stimulating the maturation of dendritic cells. Int Immunopharmacol. 2014;19(1):10–16. doi:10.1016/j.intimp.2013.12.022.
  • Welters MJ, Van Der Sluis TC, Van Meir H, Loof NM, Van Ham VJ, Van Duikeren S, Santegoets SJ, Arens R, De Kam ML, Cohen AF, et al. Vaccination during myeloid cell depletion by cancer chemotherapy fosters robust T cell responses. Sci Transl Med. 2016;8:334. doi:10.1126/scitranslmed.aad8307.