Enhancing the treatment effect on melanoma by heat shock protein 70-peptide complexes purified from human melanoma cell lines

Gao,Yanwei; Gao,Weishi; Chen,Xia; Cha,Nier; Wang,Xiaoli; Jia,Xiangdong; Wang,Bingping; Ren,Meng; Ren,Jun

doi:10.3892/or.2016.4947

Enhancing the treatment effect on melanoma by heat shock protein 70-peptide complexes purified from human melanoma cell lines

Authors:
- Yanwei Gao
- Weishi Gao
- Xia Chen
- Nier Cha
- Xiaoli Wang
- Xiangdong Jia
- Bingping Wang
- Meng Ren
- Jun Ren
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Affiliations: Cancer Center, Beijing Key Lab of Therapeutic Cancer Vaccines, Affiliated Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, P.R. China, Department of Oncology, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia 010017, P.R. China, Inner Mongolia Red Cross Blood Center, Hohhot, Inner Mongolia 010010, P.R. China
Published online on: July 19, 2016 https://doi.org/10.3892/or.2016.4947
Pages: 1243-1250
Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Dendritic cell (DC) vaccines are currently one of the most effective approaches to treat melanoma. The immunogenicity of antigens loaded into DCs determines the treatment effects. Patients treated with autologous antigen-loaded DC vaccines achieve the best therapeutic effects. In China, most melanoma patients cannot access their autologous antigens because of formalin treatment of tumor tissue after surgery. In the present study, we purified heat shock protein 70 (HSP70)-peptide complexes (PCs) from human melanoma cell lines A375, A875, M21, M14, WM‑35, and SK‑HEL‑1. We named the purified product as M‑HSP70‑PCs, and determined its immunological activities. Autologous HSP70‑PCs purified from primary tumor cells of melanoma patients (nine cases) were used as controls. These two kinds of tumor antigenic complexes loaded into DCs were used to stimulate an antitumor response against tumor cells in the corresponding patients. Mature DCs pulsed with M‑HSP70‑PCs stimulated autologous T cells to secrete the same levels of type I cytokines compared with the autologous HSP70‑PCs. Moreover, DCs pulsed with M‑HSP70‑PCs induced CD8+ T cells with an equal ability to kill melanoma cells from patients compared with autologous HSP70‑PCs. Next, we used these PC‑pulsed autologous DCs and induced autologous specific CD8+ T cells to treat one patient with melanoma of the nasal skin and lung metastasis. The treatment achieved a good effect after six cycles. These findings provide a new direction for DC-based immunotherapy for melanoma patients who cannot access autologous antigens.

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1	Kim JS, Kim YG, Pyo M, Lee HK, Hong JT, Kim Y and Han SB: Adoptive cell therapy of melanoma with cytokine-induced killer cells. Immune Netw. 15:58–65. 2015. View Article : Google Scholar : PubMed/NCBI
2	Ko JM and Fisher DE: A new era: Melanoma genetics and therapeutics. J Pathol. 223:241–250. 2011. View Article : Google Scholar
3	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2016. CA Cancer J Clin. 66:7–30. 2016. View Article : Google Scholar : PubMed/NCBI
4	Oshita C, Takikawa M, Kume A, Miyata H, Ashizawa T, Iizuka A, Kiyohara Y, Yoshikawa S, Tanosaki R, Yamazaki N, et al: Dendritic cell-based vaccination in metastatic melanoma patients: Phase II clinical trial. Oncol Rep. 28:1131–1138. 2012.PubMed/NCBI
5	Nakai N, Hartmann G, Kishimoto S and Katoh N: Dendritic cell vaccination in human melanoma: Relationships between clinical effects and vaccine parameters. Pigment Cell Melanoma Res. 23:607–619. 2010. View Article : Google Scholar : PubMed/NCBI
6	Hussein MR: Dendritic cells and melanoma tumorigenesis: An insight. Cancer Biol Ther. 4:501–505. 2005. View Article : Google Scholar : PubMed/NCBI
7	Tagliamonte M, Petrizzo A, Tornesello ML, Buonaguro FM and Buonaguro L: Antigen-specific vaccines for cancer treatment. Hum Vaccin Immunother. 10:3332–3346. 2014. View Article : Google Scholar : PubMed/NCBI
8	Ranieri E, Kierstead LS, Zarour H, Kirkwood JM, Lotze MT, Whiteside T and Storkus WJ: Dendritic cell/peptide cancer vaccines: Clinical responsiveness and epitope spreading. Immunol Invest. 29:121–125. 2000. View Article : Google Scholar : PubMed/NCBI
9	Hightower LE: Heat shock, stress proteins, chaperones, and proteotoxicity. Cell. 66:191–197. 1991. View Article : Google Scholar : PubMed/NCBI
10	Srivastava PK: Peptide-binding heat shock proteins in the endoplasmic reticulum: Role in immune response to cancer and in antigen presentation. Adv Cancer Res. 62:153–177. 1993. View Article : Google Scholar : PubMed/NCBI
11	Sherman M and Multhoff G: Heat shock proteins in cancer. Ann NY Acad Sci. 1113:192–201. 2007. View Article : Google Scholar : PubMed/NCBI
12	Gao Y, Chen X, Gao W, Yang Y, Ma H and Ren X: A new purification method for enhancing the immunogenicity of heat shock protein 70-peptide complexes. Oncol Rep. 28:1977–1983. 2012.PubMed/NCBI
13	Li Y, Zhang L, Wang S, Shi P and Qu W: Optimizing dendritic cell preparation for fusion with melanoma cells. Iran J Immunol. 11:166–176. 2014.PubMed/NCBI
14	Powell KL, Stephens AS and Ralph SJ: Development of a potent melanoma vaccine capable of stimulating CD8(+) T-cells independently of dendritic cells in a mouse model. Cancer Immunol Immunother. 64:861–872. 2015. View Article : Google Scholar : PubMed/NCBI
15	Soo JK, Ross AD and Bennett DC: Isolation and culture of melanoma and naevus cells and cell lines. Methods Mol Biol. 731:141–150. 2011. View Article : Google Scholar : PubMed/NCBI
16	Thurner B, Röder C, Dieckmann D, Heuer M, Kruse M, Glaser A, Keikavoussi P, Kämpgen E, Bender A and Schuler G: Generation of large numbers of fully mature and stable dendritic cells from leukapheresis products for clinical application. J Immunol Methods. 223:1–15. 1999. View Article : Google Scholar : PubMed/NCBI
17	Grossmann KF and Margolin K: Long-term survival as a treatment benchmark in melanoma: Latest results and clinical implications. Ther Adv Med Oncol. 7:181–191. 2015. View Article : Google Scholar : PubMed/NCBI
18	Min L and Hodi FS: Anti-PD1 following ipilimumab for mucosal melanoma: Durable tumor response associated with severe hypothyroidism and rhabdomyolysis. Cancer Immunol Res. 2:15–18. 2014. View Article : Google Scholar : PubMed/NCBI
19	Merelli B, Massi D, Cattaneo L and Mandalà M: Targeting the PD1/PD-L1 axis in melanoma: Biological rationale, clinical challenges and opportunities. Crit Rev Oncol Hematol. 89:140–165. 2014. View Article : Google Scholar
20	Kurtz DM and Gambhir SS: Tracking cellular and immune therapies in cancer. Adv Cancer Res. 124:257–296. 2014. View Article : Google Scholar : PubMed/NCBI
21	Chiang CL, Coukos G and Kandalaft LE: Whole tumor antigen vaccines: Where are we? Vaccines (Basel). 3:344–372. 2015. View Article : Google Scholar
22	Nestle FO, Alijagic S, Gilliet M, Sun Y, Grabbe S, Dummer R, Burg G and Schadendorf D: Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat Med. 4:328–332. 1998. View Article : Google Scholar : PubMed/NCBI
23	Thurner B, Haendle I, Röder C, Dieckmann D, Keikavoussi P, Jonuleit H, Bender A, Maczek C, Schreiner D, von den Driesch P, et al: Vaccination with mage-3A1 peptide-pulsed mature, monocyte-derived dendritic cells expands specific cytotoxic T cells and induces regression of some metastases in advanced stage IV melanoma. J Exp Med. 190:1669–1678. 1999. View Article : Google Scholar : PubMed/NCBI
24	Schneble EJ, Yu X, Wagner TE and Peoples GE: Novel dendritic cell-based vaccination in late stage melanoma. Hum Vaccin Immunother. 10:3132–3138. 2014. View Article : Google Scholar : PubMed/NCBI
25	Gong J, Nikrui N, Chen D, Koido S, Wu Z, Tanaka Y, Cannistra S, Avigan D and Kufe D: Fusions of human ovarian carcinoma cells with autologous or allogeneic dendritic cells induce antitumor immunity. J Immunol. 165:1705–1711. 2000. View Article : Google Scholar : PubMed/NCBI
26	Tamura Y, Peng P, Liu K, Daou M and Srivastava PK: Immunotherapy of tumors with autologous tumor-derived heat shock protein preparations. Science. 278:117–120. 1997. View Article : Google Scholar : PubMed/NCBI