B16 cell lysates plus polyinosinic-cytidylic acid effectively eradicate melanoma in a mouse model by acting as a prophylactic vaccine

Lin,Biwen; Zhao,Hua; Fan,Jianfeng; Xie,Fang; Wang,Wenjuan; Ding,Xiangyu

doi:10.3892/mmr.2014.2241

B16 cell lysates plus polyinosinic-cytidylic acid effectively eradicate melanoma in a mouse model by acting as a prophylactic vaccine

Authors:
- Biwen Lin
- Hua Zhao
- Jianfeng Fan
- Fang Xie
- Wenjuan Wang
- Xiangyu Ding
View Affiliations

Affiliations: Department of Dermatology, Chinese PLA General Hospital, Beijing 100853, P.R. China
Published online on: May 15, 2014 https://doi.org/10.3892/mmr.2014.2241
Pages: 911-916

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Th1 antigen-specific T cells secrete interferon-γ, which is able to kill antigen-specific cancer cells and is helpful for cancer vaccines. The aim of the present study was to explore whether B16 cell lysates plus polyinosinic-cytidylic acid (poly I:C) can effectively inhibit the progression of melanoma in an animal model. In the present study, C57BL/6 mice were divided into three groups, with each group containing more than six mice. The groups of mice were immunized twice with B16 cell lysates plus poly I:C, B16 cell lysates, or phosphate-buffered saline only, respectively. The in vivo results demonstrated that splenocytes from the mice immunized with B16 cell lysates plus poly I:C contained higher percentages of CD3+CD8+ T lymphocytes and CD3+CD4+ T lymphocytes, which were detected by a fluorescence-activated cell sorter, and produced higher levels of antigen-specific splenocyte proliferation activity, as detected by MTT assay. The splenocytes from the mice immunized with B16 cell lysates in combination with poly I:C produced higher levels of interferon‑γ, as detected by quantitative polymerase chain reaction and ELISA, as well as cytotoxic T lymphocyte activity when stimulated in vitro with B16 lysates. Additionally, subcutaneous immunization of the C57BL/6 mice with B16 cell lysates plus poly I:C conferred greater protection against tumor-forming B16 melanoma cells than that of the mice immunized with injection of B16 cell lysate alone. In conclusion, the cancer vaccine of B16 cell lysates plus poly I:C exerts potently protective effects that polarize responses toward Th1 and elicit antitumor immunity.

View Figures

View References

1	Lee C, Collichio F, Ollila D and Moschos S: Historical review of melanoma treatment and outcomes. Clin Dermatol. 31:141–147. 2013. View Article : Google Scholar : PubMed/NCBI
2	Chen LL, Jaimes N, Barker CA, Busam KJ and Marghoob AA: Desmoplastic melanoma: a review. J Am Acad Dermatol. 68:825–833. 2013. View Article : Google Scholar : PubMed/NCBI
3	Vourc’h-Jourdain M, Martin L and Barbarot S; aRED. Large congenital melanocytic nevi: therapeutic management and melanoma risk: a systematic review. J Am Acad Dermatol. 68:493–498. 2013.PubMed/NCBI
4	Ma C and Armstrong AW: Severe adverse events from the treatment of advanced melanoma: a systematic review of severe side effects associated with ipilimumab, vemurafenib, interferon alfa-2b, dacarbazine and interleukin-2. J Dermatolog Treat. 25:401–408. 2014. View Article : Google Scholar
5	Singh S, Nagpal SJ, Murad MH, et al: Inflammatory bowel disease is associated with an increased risk of melanoma: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 12:210–218. 2014. View Article : Google Scholar : PubMed/NCBI
6	Gogas H, Polyzos A and Kirkwood J: Immunotherapy for advanced melanoma: fulfilling the promise. Cancer Treat Rev. 39:879–885. 2013. View Article : Google Scholar : PubMed/NCBI
7	Engell-Noerregaard L, Hansen TH, Andersen MH, Thor Straten P and Svane IM: Review of clinical studies on dendritic cell-based vaccination of patients with malignant melanoma: assessment of correlation between clinical response and vaccine parameters. Cancer Immunol Immunother. 58:1–14. 2009. View Article : Google Scholar
8	Zhang S, Wang Q and Miao B: Review: dendritic cell-based vaccine in the treatment of patients with advanced melanoma. Cancer Biother Radiopharm. 22:501–507. 2007. View Article : Google Scholar : PubMed/NCBI
9	Harris RC, Chianese-Bullock KA, Petroni GR, et al: The vaccine-site microenvironment induced by injection of incomplete Freund’s adjuvant, with or without melanoma peptides. J Immunother. 35:78–88. 2012.PubMed/NCBI
10	Cho DY, Yang WK, Lee HC, et al: Adjuvant immunotherapy with whole-cell lysate dendritic cells vaccine for glioblastoma multiforme: a phase II clinical trial. World Neurosurg. 77:736–744. 2012. View Article : Google Scholar : PubMed/NCBI
11	Wang ZY, Xing Y, Liu B, et al: Protective antitumor immunity induced by tumor cell lysates conjugated with diphtheria toxin and adjuvant epitope in mouse breast tumor models. Chin J Cancer. 31:295–305. 2012. View Article : Google Scholar
12	Cui Z and Qiu F: Synthetic double-stranded RNA poly(I:C) as a potent peptide vaccine adjuvant: therapeutic activity against human cervical cancer in a rodent model. Cancer Immunol Immunother. 55:1267–1279. 2006. View Article : Google Scholar
13	Kato A, Truong-Tran AQ, Scott AL, Matsumoto K and Schleimer RP: Airway epithelial cells produce B cell-activating factor of TNF family by an IFN-beta-dependent mechanism. J Immunol. 177:7164–7172. 2006. View Article : Google Scholar : PubMed/NCBI
14	Inao T, Harashima N, Monma H, et al: Antitumor effects of cytoplasmic delivery of an innate adjuvant receptor ligand, poly(I:C), on human breast cancer. Breast Cancer Res Treat. 134:89–100. 2012. View Article : Google Scholar : PubMed/NCBI
15	Rajan JV, Warren SE, Miao EA and Aderem A: Activation of the NLRP3 inflammasome by intracellular poly I:C. FEBS Lett. 584:4627–4632. 2010. View Article : Google Scholar : PubMed/NCBI
16	Trumpfheller C, Caskey M, Nchinda G, et al: The microbial mimic poly IC induces durable and protective CD4⁺ T cell immunity together with a dendritic cell targeted vaccine. Proc Natl Acad Sci USA. 105:2574–2579. 2008. View Article : Google Scholar : PubMed/NCBI
17	Wörnle M, Sauter M, Kastenmüller K, et al: Novel role of toll-like receptor 3, RIG-I and MDA5 in poly (I:C) RNA-induced mesothelial inflammation. Mol Cell Biochem. 322:193–206. 2009.
18	Longhi MP, Trumpfheller C, Idoyaga J, et al: Dendritic cells require a systemic type I interferon response to mature and induce CD4⁺ Th1 immunity with poly IC as adjuvant. J Exp Med. 206:1589–1602. 2009. View Article : Google Scholar : PubMed/NCBI
19	Bose A, Lowe DB, Rao A and Storkus WJ: Combined vaccine+axitinib therapy yields superior antitumor efficacy in a murine melanoma model. Melanoma Res. 22:236–243. 2012. View Article : Google Scholar : PubMed/NCBI
20	Kayaga J, Souberbielle BE, Sheikh N, et al: Anti-tumour activity against B16-F10 melanoma with a GM-CSF secreting allogeneic tumour cell vaccine. Gene Ther. 6:1475–1481. 1999. View Article : Google Scholar
21	Mosmann T: Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 65:55–63. 1983. View Article : Google Scholar : PubMed/NCBI
22	Kirkwood JM, Moschos S and Wang W: Strategies for the development of more effective adjuvant therapy of melanoma: current and future explorations of antibodies, cytokines, vaccines, and combinations. Clin Cancer Res. 12:2331s–2336s. 2006. View Article : Google Scholar : PubMed/NCBI
23	Kirkwood JM, Strawderman MH, Ernstoff MS, Smith TJ, Borden EC and Blum RH: Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. J Clin Oncol. 14:7–17. 1996.PubMed/NCBI
24	Terando A, Sabel MS and Sondak VK: Melanoma: adjuvant therapy and other treatment options. Curr Treat Options Oncol. 4:187–199. 2003. View Article : Google Scholar : PubMed/NCBI
25	Krishnan L, Deschatelets L, Stark FC, Gurnani K and Sprott GD: Archaeosome adjuvant overcomes tolerance to tumor-associated melanoma antigens inducing protective CD8 T cell responses. Clin Dev Immunol. 2010:5784322010. View Article : Google Scholar
26	Mechl Z and Kopecný J: Current results with surgery and adjuvant chemotherapy in malignant melanoma. Arch Geschwulstforsch. 56:367–371. 1986.(In German).
27	Olivier A, Sainz-Perez A, Dong H, Sparwasser T, Majlessi L and Leclerc C: The adjuvant effect of TLR agonists on CD4(+) effector T cells is under the indirect control of regulatory T cells. Eur J Immunol. 41:2303–2313. 2011. View Article : Google Scholar : PubMed/NCBI
28	Huang YK, Zheng Z, Cheng CX, Wang LY, Li YR and Qiu F: The antitumor effect of the toll-like receptor 3 ligand polyinosinic-cytidylic acid as an adjuvant. Cancer Immunol Immunother. 62:237–244. 2013. View Article : Google Scholar : PubMed/NCBI
29	Martínez-Gil L, Goff PH, Hai R, García-Sastre A, Shaw ML and Palese P: A Sendai virus-derived RNA agonist of RIG-I as a virus vaccine adjuvant. J Virol. 87:1290–1300. 2013.PubMed/NCBI
30	Wang S, Du W, Zhang H, et al: Biological characteristics and antitumor activity of CIK cells activated by recombinant human fibronectin for human lung cancer cell lines in vitro. Zhongguo Fei Ai Za Zhi. 13:277–281. 2010.PubMed/NCBI
31	Starska K, Głowacka E, Kulig A, Lewy-Trenda I, Bryś M and Lewkowicz P: The role of tumor cells in the modification of T lymphocytes activity - the expression of the early CD69⁺, CD71⁺ and the late CD25⁺, CD26⁺, HLA/DR⁺ activation markers on T CD4⁺ and CD8⁺ cells in squamous cell laryngeal carcinoma. Part I Folia Histochem Cytobiol. 49:579–592. 2011.PubMed/NCBI
32	Török L: Adjuvant interferon treatment of melanoma. Magy Onkol. 47:105–107. 2003.(In Hungarian).
33	Mitchell MS, Kan-Mitchell J, Kempf RA, Harel W, Shau HY and Lind S: Active specific immunotherapy for melanoma: phase I trial of allogeneic lysates and a novel adjuvant. Cancer Res. 48:5883–5893. 1988.PubMed/NCBI
34	Jasani B, Navabi H and Adams M: Ampligen: a potential toll-like 3 receptor adjuvant for immunotherapy of cancer. Vaccine. 27:3401–3404. 2009. View Article : Google Scholar : PubMed/NCBI
35	May M, Kendel F, Hoschke B, et al: Adjuvant autologous tumour cell vaccination in patients with renal cell carcinoma. Overall survival analysis with a follow-up period in excess of more than 10 years. Urologe A. 48:1075–1083. 2009.(In German).
36	May M, Brookman-May S, Hoschke B, et al: Ten-year survival analysis for renal carcinoma patients treated with an autologous tumour lysate vaccine in an adjuvant setting. Cancer Immunol Immunother. 59:687–695. 2010.
37	Markowicz S, Nowecki ZI, Rutkowski P, et al: Adjuvant vaccination with melanoma antigen-pulsed dendritic cells in stage III melanoma patients. Med Oncol. 29:2966–2977. 2012. View Article : Google Scholar : PubMed/NCBI