Inhibition of prostate cancer growth by immunization with a GM-CSF-modified mouse prostate cancer RM‑1 cell vaccine in a novel murine model

Xia,Hongmei; Luo,Xiaojing; Yin,Weihua

doi:10.3892/ol.2017.7332

Inhibition of prostate cancer growth by immunization with a GM-CSF-modified mouse prostate cancer RM‑1 cell vaccine in a novel murine model

Authors:
- Hongmei Xia
- Xiaojing Luo
- Weihua Yin
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Affiliations: Department of Oncology, The People's Hospital of Yichun Affiliated to Clinical Medicine School of Yichun University in Jiangxi Province, Yichun, Jiangxi 336000, P.R. China
Published online on: November 2, 2017 https://doi.org/10.3892/ol.2017.7332
Pages: 538-544

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Abstract

Advanced prostate cancer is difficult to treat owing to a lack of effective approaches for disrupting immune tolerance. C57BL/6 male and female mice implanted with viable RM‑1 cells represent a novel murine model of advanced prostate cancer for studying antitumor effects following immunization with a granulocyte‑macrophage colony‑stimulating factor (GM‑CSF)‑modified RM‑1 cell vaccine, which has been described previously. In vitro cytotoxic activity and cytokine secretion experiments were conducted to investigate the antitumor response. The cytotoxicity profile of splenocytes from female mice immunized against RM‑1 cells primarily involved cytotoxic T lymphocyte (CTL) lysis and, to a lesser extent, natural killer (NK) cell lysis. NK cell lysis was also observed in males, which exhibited no evidence of CTL lysis. The secretion of interferon‑γ in the GM‑CSF‑modified cell vaccine group was significantly increased compared with the other groups. The level of interleukin‑4 was low. To investigate the antitumor immune response further, cluster of differentiation 4 (CD4) T cells and CD8 T cells were analyzed in the spleens and tumors of female mice receiving the GM‑CSF‑modified RM‑1 cell vaccine. Unlike female mice, males exhibited the highest proportion of NK cells in the spleen. NK cells were not detected in the tumor tissue in any of the groups. The difference between the sexes may explain the specificity of the immune response, as females are intolerant to prostate antigens whereas males are. This model is clinically relevant as it translates to human immunology and offers an effective and convenient method for studying immunotherapy for prostate cancer.

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1	Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI
2	Crawford ED, Blumenstein BA, Goodman PJ, Davis MA, Eisenberger MA, McLeod DG, Spaulding JT, Benson R and Dorr FA: Leuprolide with and without flutamide in advanced prostate cancer. Cancer. 66(5 Suppl): S1039–S1044. 1990. View Article : Google Scholar
3	Quinn DI, Tangen CM, Hussain M, Lara PN Jr, Goldkorn A, Moinpour CM, Garzotto MG, Mack PC, Carducci MA, Monk JP, et al: Docetaxel and atrasentan versus docetaxel and placebo for men with advanced castration-resistant prostate cancer (SWOG S0421): A randomised phase 3 trial. Lancet Oncol. 14:893–900. 2013. View Article : Google Scholar : PubMed/NCBI
4	Armstrong AJ and Carducci MA: Chemotherapy for advanced prostate cancer: Results of new clinical trials and future studies. Curr Oncol Rep. 7:220–227. 2005. View Article : Google Scholar : PubMed/NCBI
5	Haigh PI, Difronzo LA, Gammon G and Morton DL: Vaccine therapy for patients with melanoma. Oncology (Williston Park). 13:1561–1574. 1999.PubMed/NCBI
6	Li H, Jiang HJ, Ma MQ, Wei F, An XM and Ren XB: Vaccination with allogeneic GM-CSF gene-modified lung cancer cells: Antitumor activity comparing with that induced by autologous vaccine. Cancer Biother Radiopharm. 22:790–798. 2007. View Article : Google Scholar : PubMed/NCBI
7	Obata C, Zhang M, Moroi Y, Hisaeda H, Tanaka K, Murata S, Furue M and Himeno K: Formalin-fixed tumor cells effectively induce antitumor immunity both in prophylactic and therapeutic conditions. J Dermatol Sci. 34:209–219. 2004. View Article : Google Scholar : PubMed/NCBI
8	Yin W, He Q, Hu Z, Chen Z, Qifeng M, Zhichun S, Zhihui Q, Xiaoxia N, Li J and Gao J: A novel therapeutic vaccine of GM-CSF/TNFalpha surface-modified RM-1 cells against the orthotopic prostatic cancer. Vaccine. 28:4937–4944. 2010. View Article : Google Scholar : PubMed/NCBI
9	Suckow MA, Wolter WR and Pollard M: Prevention of de novo prostate cancer by immunization with tumor-derived vaccines. Cancer Immunol Immunother. 54:571–576. 2005. View Article : Google Scholar : PubMed/NCBI
10	Kotera Y, Shimizu K and Mulé JJ: Comparative analysis of necrotic and apoptotic tumor cells as a source of antigen(s) in dendritic cell-based immunization. Cancer Res. 61:8105–8109. 2001.PubMed/NCBI
11	Ahram M, Flaig MJ, Gillespie JW, Duray PH, Linehan WM, Ornstein DK, Niu S, Zhao Y, Petricoin EF III and Emmert-Buck MR: Evaluation of ethanol-fixed, paraffin-embedded tissues for proteomic applications. Proteomics. 3:413–421. 2003. View Article : Google Scholar : PubMed/NCBI
12	Baley PA, Yoshida K, Qian W, Sehgal I and Thompson TC: Progression to androgen insensitivity in a novel in vitro mouse model for prostate cancer. J Steroid Biochem Mol Biol. 52:403–413. 1995. View Article : Google Scholar : PubMed/NCBI
13	Griffith TS, Kawakita M, Tian J, Ritchey J, Tartaglia J, Sehgal I, Thompson TC, Zhao W and Ratliff TL: Inhibition of murine prostate tumor growth and activation of immunoregulatory cells with recombinant canarypox viruses. J Natl Cancer Inst. 93:998–1007. 2001. View Article : Google Scholar : PubMed/NCBI
14	Labarthe MC, Theocharous P, Russell N, Todryk S, Bangma C, Thraves P, Dalgleish AG and Whelan MA: A novel murine model of allogeneic vaccination against prostate cancer. Cancer Immunol Immunother. 57:453–465. 2008. View Article : Google Scholar : PubMed/NCBI
15	He Q, Li J, Yin W, Song Z, Zhang Z, Yi T, Tang J, Wu D, Lu Y, Wang Z, et al: Low-dose paclitaxel enhances the anti-tumor efficacy of GM-CSF surface-modified whole-tumor-cell vaccine in mouse model of prostate cancer. Cancer Immunol Immunother. 60:715–730. 2011. View Article : Google Scholar : PubMed/NCBI
16	Cooper MD and Alder MN: The evolution of adaptive immune systems. Cell. 124:815–822. 2006. View Article : Google Scholar : PubMed/NCBI
17	Li M, Davey GM, Sutherland RM, Kurts C, Lew AM, Hirst C, Carbone FR and Heath WR: Cell-associated ovalbumin is cross-presented much more efficiently than soluble ovalbumin in vivo. J Immunol. 166:6099–6103. 2001. View Article : Google Scholar : PubMed/NCBI
18	Gallucci S, Lolkema M and Matzinger P: Natural adjuvants: Endogenous activators of dendritic cells. Nat Med. 5:1249–1255. 1999. View Article : Google Scholar : PubMed/NCBI
19	Sauter B, Albert ML, Francisco L, Larsson M, Somersan S and Bhardwaj N: Consequences of cell death: Exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells. J Exp Med. 191:423–434. 2000. View Article : Google Scholar : PubMed/NCBI
20	Grant JF, Iwasawa T, Sinn HW, Siemens DR, Griffith TS, Takacs EB and Ratliff TL: Induction of protective immunity to RM-1 prostate cancer cells with ALVAC-IL-2/IL-12/TNF-alpha combination therapy. Int J Cancer. 119:2632–2641. 2006. View Article : Google Scholar : PubMed/NCBI
21	Carbone FR, Kurts C, Bennett SR, Miller JF and Heath WR: Cross-presentation: A general mechanism for CTL immunity and tolerance. Immunol Today. 19:368–373. 1998. View Article : Google Scholar : PubMed/NCBI
22	Chhikara M, Huang H, Vlachaki MT, Zhu X, Teh B, Chiu KJ, Woo S, Berner B, Smith EO, Oberg KC, et al: Enhanced therapeutic effect of HSV-tk+GCV gene therapy and ionizing radiation for prostate cancer. Mol Ther. 3:536–542. 2001. View Article : Google Scholar : PubMed/NCBI
23	Schroten-Loef C, de Ridder CM, Reneman S, Crezee M, Dalgleish A, Todryk SM, Bangma CH and Kraaij R: A prostate cancer vaccine comprising whole cells secreting IL-7, effective against subcutaneous challenge, requires local GM-CSF for intra-prostatic efficacy. Cancer Immunol Immunother. 58:373–381. 2009. View Article : Google Scholar : PubMed/NCBI