Abstract
We have developed an enhanced molecular chaperone-based vaccine through rapid isolation of Hsp70 peptide complexes after the fusion of tumor and dendritic cells (Hsp70.PC-F). In this approach, the tumor antigens are introduced into the antigen processing machinery of dendritic cells through the cell fusion process and thus we can obtain antigenic tumor peptides or their intermediates that have been processed by dendritic cells. Our results show that Hsp70.PC-F has increased immunogenicity compared to preparations from tumor cells alone and therefore constitutes an improved formulation of chaperone protein-based tumor vaccine.
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References
Lindquist S, Craig EA (1988) The heat shock proteins. Ann Rev Genet 22:631–637
Georgopolis C, Welch WJ (1993) Role of the major heat shock proteins as molecular chaperones. Ann Rev Cell Biol 9:601–634
Richter K, Haslbeck M, Buchner J (2010) The heat shock response: life on the verge of death. Mol Cell 40(2):253–266
Bukau B, Horwich AL (1998) The Hsp70 and Hsp60 chaperone machines. Cell 92(3):351–366
Tang D et al (2005) Expression of heat shock proteins and HSP messenger ribonucleic acid in human prostate carcinoma in vitro and in tumors in vivo. Cell Stress Chaperones 10:46–58
Kityk R et al (2015) Pathways of allosteric regulation in Hsp70 chaperones. Nat Commun 6:8308
Noessner E et al (2002) Tumor-derived heat shock protein 70 peptide complexes are cross-presented by human dendritic cells. J Immunol 169(10):5424–5432
Srivastava PK, Amato RJ (2001) Heat shock proteins: the ‘Swiss Army Knife’ vaccines against cancers and infectious agents. Vaccine 19(17–19):2590–2597
Nylandsted J, Brand K, Jaattela M (2000) Heat shock protein 70 is required for the survival of cancer cells. Ann N Y Acad Sci 926:122–125
Cornford PA et al (2000) Heat shock protein expression independently predicts clinical outcome in prostate cancer. Cancer Res 60(24):7099–7105
Clark PR, Menoret A (2001) The inducible Hsp70 as a marker of tumor immunogenicity. Cell Stress Chaperones 6(2):121–125
Calderwood SK, Gong J (2016) Heat shock proteins promote cancer: it’s a protection racket. Trends Biochem Sci 41:311–323
Srivastava P (2002) Interaction of heat shock proteins with peptides and antigen presenting cells: chaperoning of the innate and adaptive immune responses. Annu Rev Immunol 20:395–425
Srivastava P (2003) Hypothesis: controlled necrosis as a tool for immunotherapy of human cancer. Cancer Immun 3:4
Srivastava PK (2000) Immunotherapy of human cancer: lessons from mice. Nat Immunol 1(5):363–366
Belli F et al (2002) Vaccination of metastatic melanoma patients with autologous tumor-derived heat shock protein gp96-peptide complexes: clinical and immunologic findings. J Clin Oncol 20(20):4169–4180
Mazzaferro V et al (2003) Vaccination with autologous tumor-derived heat-shock protein gp96 after liver resection for metastatic colorectal cancer. Clin Cancer Res 9(9):3235–3245
Parmiani G et al (2006) Heat shock proteins gp96 as immunogens in cancer patients. Int J Hyperth 22(3):223–227
Pilla L et al (2006) A phase II trial of vaccination with autologous, tumor-derived heat-shock protein peptide complexes Gp96, in combination with GM-CSF and interferon-alpha in metastatic melanoma patients. Cancer Immunol Immunother 55(8):958–968
Testori A et al (2008) Phase III comparison of vitespen, an autologous tumor-derived heat shock protein gp96 peptide complex vaccine, with physician's choice of treatment for stage IV melanoma: the C-100-21 Study Group. J Clin Oncol 26(6):955–962
Wood C et al (2008) An adjuvant autologous therapeutic vaccine (HSPPC-96; vitespen) versus observation alone for patients at high risk of recurrence after nephrectomy for renal cell carcinoma: a multicentre, open-label, randomised phase III trial. Lancet 372(9633):145–154
Enomoto Y et al (2006) Enhanced immunogenicity of heat shock protein 70 peptide complexes from dendritic cell-tumor fusion cells. J Immunol 177(9):5946–5955
Weng D et al (2013) Immunotherapy of radioresistant mammary tumors with early metastasis using molecular chaperone vaccines combined with ionizing radiation. J Immunol 191(2):755–763
Steinman RM (1991) The dendritic cell system and its role in immunogenicity. Annu Rev Immunol 9:271–296
Steinman RM (2001) Dendritic cells and the control of immunity: enhancing the efficiency of antigen presentation. Mt Sinai J Med 68(3):106–166
Gong J et al (1997) Induction of antitumor activity by immunization with fusions of dendritic and carcinoma cells. Nat Med 3(5):558–561
Gong J et al (2002) Immunization against murine multiple myeloma with fusions of dendritic and plasmacytoma cells is potentiated by interleukin 12. Blood 99(7):2512–2517
Liu Y et al (2002) Engineered fusion hybrid vaccine of IL-4 gene-modified myeloma and relative mature dendritic cells enhances antitumor immunity. Leuk Res 26(8):757–763
Lindner M, Schirrmacher V (2002) Tumour cell-dendritic cell fusion for cancer immunotherapy: comparison of therapeutic efficiency of polyethylen-glycol versus electro-fusion protocols. Eur J Clin Investig 32(3):207–217
Homma S et al (2001) Preventive antitumor activity against hepatocellular carcinoma (HCC) induced by immunization with fusions of dendritic cells and HCC cells in mice. J Gastroenterol 36(11):764–771
Cao X et al (1999) Therapy of established tumour with a hybrid cellular vaccine generated by using granulocyte-macrophage colony-stimulating factor genetically modified dendritic cells. Immunology 97(4):616–625
Wang J et al (1998) Eliciting T cell immunity against poorly immunogenic tumors by immunization with dendritic cell-tumor fusion vaccines. J Immunol 161(10):5516–5524
Hayashi T et al (2002) Immunogenicity and therapeutic efficacy of dendritic-tumor hybrid cells generated by electrofusion. Clin Immunol 104(1):14–20
Xia J et al (2003) Prevention of spontaneous breast carcinoma by prophylactic vaccination with dendritic/tumor fusion cells. J Immunol 170(4):1980–1986
Kao JY et al (2003) Tumor-derived TGF-beta reduces the efficacy of dendritic cell/tumor fusion vaccine. J Immunol 170(7):3806–3811
Takeda A et al (2003) Immature dendritic cell/tumor cell fusions induce potent antitumour immunity. Eur J Clin Investig 33(10):897–904
Zhang JK et al (2003) Antitumor immunopreventive and immunotherapeutic effect in mice induced by hybrid vaccine of dendritic cells and hepatocarcinoma in vivo. World J Gastroenterol 9(3):479–484
Li J et al (2001) Purified hybrid cells from dendritic cell and tumor cell fusions are superior activators of antitumor immunity. Cancer Immunol Immunother 50(9):456–462
Xia D, Chan T, Xiang J (2005) Dendritic cell/myeloma hybrid vaccine. Methods Mol Med 113:225–233
Homma S et al (2005) Cancer immunotherapy by fusions of dendritic and tumour cells and rh-IL-12. Eur J Clin Investig 35(4):279–286
Kao JY et al (2005) Superior efficacy of dendritic cell-tumor fusion vaccine compared with tumor lysate-pulsed dendritic cell vaccine in colon cancer. Immunol Lett 101(2):154–159
Ogawa F, Iinuma H, Okinaga K (2004) Dendritic cell vaccine therapy by immunization with fusion cells of interleukin-2 gene-transduced, spleen-derived dendritic cells and tumour cells. Scand J Immunol 59(5):432–439
Akasaki Y et al (2001) Antitumor effect of immunizations with fusions of dendritic and glioma cells in a mouse brain tumor model. J Immunother 24(2):106–113
Scott-Taylor TH et al (2000) Human tumour and dendritic cell hybrids generated by electrofusion: potential for cancer vaccines. Biochim Biophys Acta 1500(3):265–279
Tanaka H et al (2002) Therapeutic immune response induced by electrofusion of dendritic and tumor cells. Cell Immunol 220(1):1–12
Siders WM et al (2003) Induction of specific antitumor immunity in the mouse with the electrofusion product of tumor cells and dendritic cells. Mol Ther 7(4):498–505
Jantscheff P et al (2002) Cell fusion: an approach to generating constitutively proliferating human tumor antigen-presenting cells. Cancer Immunol Immunother 51(7):367–375
Goddard RV et al (2003) In vitro dendritic cell-induced T cell responses to B cell chronic lymphocytic leukaemia enhanced by IL-15 and dendritic cell-B-CLL electrofusion hybrids. Clin Exp Immunol 131(1):82–89
Marten A et al (2003) Allogeneic dendritic cells fused with tumor cells: preclinical results and outcome of a clinical phase I/II trial in patients with metastatic renal cell carcinoma. Hum Gene Ther 14(5):483–494
Trevor KT et al (2004) Generation of dendritic cell-tumor cell hybrids by electrofusion for clinical vaccine application. Cancer Immunol Immunother 53(8):705–714
Suzuki T et al (2005) Vaccination of dendritic cells loaded with interleukin-12-secreting cancer cells augments in vivo antitumor immunity: characteristics of syngeneic and allogeneic antigen-presenting cell cancer hybrid cells. Clin Cancer Res 11(1):58–66
Trefzer U et al (2005) Tumour-dendritic hybrid cell vaccination for the treatment of patients with malignant melanoma: immunological effects and clinical results. Vaccine 23(17–18):2367–2373
Shimizu K et al (2004) Comparative analysis of antigen loading strategies of dendritic cells for tumor immunotherapy. J Immunother 27(4):265–272
Phan V et al (2003) A new genetic method to generate and isolate small, short-lived but highly potent dendritic cell-tumor cell hybrid vaccines. Nat Med 9(9):1215–1219
Hiraoka K et al (2004) Enhanced tumor-specific long-term immunity of hemagglutinating [correction of hemaggluttinating] virus of Japan-mediated dendritic cell-tumor fused cell vaccination by coadministration with CpG oligodeoxynucleotides. J Immunol 173(7):4297–4307
Koido S et al (2004) Dendritic cells fused with human cancer cells: morphology, antigen expression, and T cell stimulation. Clin Immunol 113(3):261–269
Galea-Lauri J et al (2002) Eliciting cytotoxic T lymphocytes against acute myeloid leukemia-derived antigens: evaluation of dendritic cell-leukemia cell hybrids and other antigen-loading strategies for dendritic cell-based vaccination. Cancer Immunol Immunother 51(6):299–310
Gong J et al (2000) Fusions of human ovarian carcinoma cells with autologous or allogeneic dendritic cells induce antitumor immunity. J Immunol 165(3):1705–1711
Gong J et al (2000) Activation of antitumor cytotoxic T lymphocytes by fusions of human dendritic cells and breast carcinoma cells. Proc Natl Acad Sci U S A 97(6):2715–2718
Koido S et al (2005) Assessment of fusion cells from patient-derived ovarian carcinoma cells and dendritic cells as a vaccine for clinical use. Gynecol Oncol 99(2):462–471
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Weng, D., Calderwood, S.K., Gong, J. (2018). A Novel Heat Shock Protein 70-based Vaccine Prepared from DC-Tumor Fusion Cells. In: Calderwood, S., Prince, T. (eds) Chaperones. Methods in Molecular Biology, vol 1709. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7477-1_26
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DOI: https://doi.org/10.1007/978-1-4939-7477-1_26
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