CD80-pIRES-SART3真核表达载体的构建
|
摘要
目的:构建CD80-pIRES-SART3真核表达载体。
方法:首先用RT-PCR技术扩增出小鼠的CD80基因片段全长并在其两端加上酶切位点EcoR I,琼脂糖凝胶电泳并进行胶回收,纯化扩增出来的CD80目的基因片段,用同源重组技术将其插入线性化的真核表达载体pIRES的多克隆位点的EcoR I酶切位点中,转化感受态细胞,挑选阳性克隆株并大量扩增,提取阳性克隆株的质粒,通过PCR技术、双酶切以及测序检测CD80基因的插入情况;然后以PCR技术扩增出SART3全长基因片段并在其两端加上酶切位点Xba I,琼脂糖凝胶电泳并进行胶回收,纯化扩增出来的SART3目的基因片段,用同源重组技术将SART3基因插入真核表达载体CD80-pIRES上的Xba I酶切位点中,转化感受态细胞,挑选阳性克隆株并大量扩增,提取阳性克隆株的质粒,通过PCR技术、双酶切以及测序检测SART3基因的插入情况。
结果: 1.成功提取小鼠脾脏的RNA并逆转录成cDNA,利用合成的引物扩增出小鼠CD80基因序列全长。2.成功将CD80基因片段插入pIRES真核表达载体多克隆位点的EcoR I酶切位点中,构建出CD80-pIRES真核表达载体。3.利用合成的引物成功扩增出SART3基因序列全长。4.成功将SART3基因片段插入CD80-pIRES真核表达载体中的Xba I酶切位点上,构建出CD80-pIRES-SART3真核表达载体。
结论:成功构建CD80-pIRES-SART3真核表达载体,为进一步研究其在骨肉瘤基因免疫治疗中的作用奠定了基础,为进一步研究其在相关肿瘤基因免疫治疗中的作用奠定了基础,为肿瘤基因免疫治疗提供了可供参考的方法。
Objective: Construction of eukaryotic expression vector of CD80-pIRES-SART3.
Methods: Firstly,by using RT-PCR technolgy amplify the whole fragment of CD80 gene of mouse and to add EcoR I restriction enzyme cutting site on the both ends of the gene fragment.Then purify the purpose extract of CD80 fragment after agarose gel electrophoresis and gel extraction.Next,insert the CD80 gene fragment into EcoR I restriction enzyme cutting site of the linearized eukaryotic expression vector of pIRES by homelogens DNA technology. Afterward, get the recombinant vector into competence cells and choose positive cloning strains. Aμgment the positive cloning strains and extract the plasmid from the strains. Detect the recombinant vector by PCR technology、enzyme digest and gene sequence analysis. Meanwhile,by using PCR technolgy amplify the whole fragment of SART3 gene and to add Xba I restriction enzyme cutting site on the both ends of the gene fragment. Then purify the purpose extract of SART3 fragment after agarose gel electrophoresis and gel extraction. Next,insert the SART3 gene fragment into Xba I restriction enzyme cutting site of the linearized eukaryotic expression vector of CD80-pIRES by homelogens DNA technology.Finally, get the recombinant vector into competence cells and choose positive cloning strains. Aμgment the positive cloning strains and extract the plasmid from the strains. Detect the recombinant vector by PCR technology、enzyme digest and gene sequence analysis.
ResμLts: 1.SuccessfμLly extract the RNA of mouse’s spleen and reverse transcribe the RNA into cDNA.Using synthetized primer amplify the whole fragment of CD80 gene. 2. SuccessfμLly insert the CD80 gene fragment into eukaryotic expression vector of pIRES and construct the CD80-pIRES vector.3. By using PCR technolgy amplify the whole fragment of SART3 gene.4. SuccessfμLly insert the SART3 gene fragment into eukaryotic expression vector of CD80- pIRES and construct the CD80-pIRES-SART3 vector.
Conclusion: SuccessfμLly construct the CD80-pIRES-SART3 vector.This will lay a foundation for further study of gene immunotherapy of osteosarcoma,also lay a foundation for further study of gene immunotherapy of interrelated tumour and provide a referable strategy for gene immunotherapy of tumour.
方法:首先用RT-PCR技术扩增出小鼠的CD80基因片段全长并在其两端加上酶切位点EcoR I,琼脂糖凝胶电泳并进行胶回收,纯化扩增出来的CD80目的基因片段,用同源重组技术将其插入线性化的真核表达载体pIRES的多克隆位点的EcoR I酶切位点中,转化感受态细胞,挑选阳性克隆株并大量扩增,提取阳性克隆株的质粒,通过PCR技术、双酶切以及测序检测CD80基因的插入情况;然后以PCR技术扩增出SART3全长基因片段并在其两端加上酶切位点Xba I,琼脂糖凝胶电泳并进行胶回收,纯化扩增出来的SART3目的基因片段,用同源重组技术将SART3基因插入真核表达载体CD80-pIRES上的Xba I酶切位点中,转化感受态细胞,挑选阳性克隆株并大量扩增,提取阳性克隆株的质粒,通过PCR技术、双酶切以及测序检测SART3基因的插入情况。
结果: 1.成功提取小鼠脾脏的RNA并逆转录成cDNA,利用合成的引物扩增出小鼠CD80基因序列全长。2.成功将CD80基因片段插入pIRES真核表达载体多克隆位点的EcoR I酶切位点中,构建出CD80-pIRES真核表达载体。3.利用合成的引物成功扩增出SART3基因序列全长。4.成功将SART3基因片段插入CD80-pIRES真核表达载体中的Xba I酶切位点上,构建出CD80-pIRES-SART3真核表达载体。
结论:成功构建CD80-pIRES-SART3真核表达载体,为进一步研究其在骨肉瘤基因免疫治疗中的作用奠定了基础,为进一步研究其在相关肿瘤基因免疫治疗中的作用奠定了基础,为肿瘤基因免疫治疗提供了可供参考的方法。
Objective: Construction of eukaryotic expression vector of CD80-pIRES-SART3.
Methods: Firstly,by using RT-PCR technolgy amplify the whole fragment of CD80 gene of mouse and to add EcoR I restriction enzyme cutting site on the both ends of the gene fragment.Then purify the purpose extract of CD80 fragment after agarose gel electrophoresis and gel extraction.Next,insert the CD80 gene fragment into EcoR I restriction enzyme cutting site of the linearized eukaryotic expression vector of pIRES by homelogens DNA technology. Afterward, get the recombinant vector into competence cells and choose positive cloning strains. Aμgment the positive cloning strains and extract the plasmid from the strains. Detect the recombinant vector by PCR technology、enzyme digest and gene sequence analysis. Meanwhile,by using PCR technolgy amplify the whole fragment of SART3 gene and to add Xba I restriction enzyme cutting site on the both ends of the gene fragment. Then purify the purpose extract of SART3 fragment after agarose gel electrophoresis and gel extraction. Next,insert the SART3 gene fragment into Xba I restriction enzyme cutting site of the linearized eukaryotic expression vector of CD80-pIRES by homelogens DNA technology.Finally, get the recombinant vector into competence cells and choose positive cloning strains. Aμgment the positive cloning strains and extract the plasmid from the strains. Detect the recombinant vector by PCR technology、enzyme digest and gene sequence analysis.
ResμLts: 1.SuccessfμLly extract the RNA of mouse’s spleen and reverse transcribe the RNA into cDNA.Using synthetized primer amplify the whole fragment of CD80 gene. 2. SuccessfμLly insert the CD80 gene fragment into eukaryotic expression vector of pIRES and construct the CD80-pIRES vector.3. By using PCR technolgy amplify the whole fragment of SART3 gene.4. SuccessfμLly insert the SART3 gene fragment into eukaryotic expression vector of CD80- pIRES and construct the CD80-pIRES-SART3 vector.
Conclusion: SuccessfμLly construct the CD80-pIRES-SART3 vector.This will lay a foundation for further study of gene immunotherapy of osteosarcoma,also lay a foundation for further study of gene immunotherapy of interrelated tumour and provide a referable strategy for gene immunotherapy of tumour.
引文
1. Rabinovich GA, Gabrilovich D, Sotomayor EM, et al. Immunosuppressive strategies that are mediated by tumor cells. Annu Rev Immunol 2007;25:267–96.
2.Tirapu I, Huarte E, Guiducci C, et al. Low surface expression of B7-1 (CD80) is an immunoescape mechanism of colon carcinoma.Cancer Res 2006;66:2442–50.
3.Kim R, Emi M, Tanabe K, et al. Cancer immunoediting from immune surveillance to immune escape. Immunology 2007;121:1–14.
4.Podhajcer OL, Lopez MV, Mazzolini G. Cytokine gene transfer for cancer therapy.Cytokine Growth Factor Rev 2007;18:183–94.
5.Copier J, Dalgleish A. Overview of tumor cell-based vaccines. Int Rev Immunol 2006;25:297–319.
6. Adepoju LJ, Geiger JD. Antitumor activity of polyuridylic acid in human soft tissue and bone sarcomas. J Surg Res. 2010 Nov;164(1):e107-14.
7.Kawano M, Nishida H, Nakamoto Y, Tsumura H, Tsuchiya H. Cryoimmunologic antitumor effects enhanced by dendritic cells in osteosarcoma. Clin Orthop Relat Res. 2010 May;468(5):1373-83.
8. Loeb DM. Is there a role for immunotherapy in osteosarcoma? Cancer Treat Res. 2009;152:447-57.
9. Ahmed N, Salsman VS, Yvon E, Louis CU, Perlaky L, Wels WS, Dishop MK,Kleinerman EE, PμLe M, Rooney CM, Heslop HE, Gottschalk S. Immunotherapy for osteosarcoma: genetic modification of T cells overcomes low levels of tumor antigen expression. Mol Ther. 2009 Oct;17(10):1779-87.
10. Sakamoto A, Iwamoto Y. Current status and perspectives regarding the treatment of osteo-sarcoma: chemotherapy. Rev Recent Clin Trials. 2008 Sep;3(3):228-31.
11. Fagioli F, Biasin E, Mereuta OM, Muraro M, Luksch R, Ferrari S, Aglietta M,Madon E. Poor prognosis osteosarcoma: new therapeutic approach. Bone Marrow Transplant. 2008 Jun;41 Suppl 2:S131-4.
12.Muraro M, Mereuta OM, Saglio F, Carraro F, Berger M, Madon E, Fagioli F.Interactions between osteosarcoma cell lines and dendritic cells immune function:An in vitro study. Cell Immunol. 2008 May-Jun;253(1-2):71-80. Epub 2008 Jun 18.
13. Erben P, Gosenca D, Müller MC, Reinhard J, Score J, Del Valle F, Walz C, Mix J, Metzgeroth G, Ernst T, Haferlach C, Cross NC, Hochhaus A, Reiter A. Screening for diverse PDGFRA or PDGFRB fusion genes is facilitated by generic quantitative reverse transcriptase polymerase chain reaction analysis. Haematologica. 2010May;95(5):738-44. Epub 2010 Jan 27.
14.Tsuda N, Murayama K, Ishida H,et al.Expression of a newly defined tumor-rejection antigen SART3 in muscμLoskeletal tumors and induction of HLA class I-restricted cytotoxic T lymphocytes by SART3-derived peptides.J Orthop Res. 2001 May;19(3):346-51.
15.Suefuji Y, Sasatomi T, Shichijo S, et al .Expression of SART3 antigen and induction of CTLs by SART3-derived peptides in breast cancer patients.Br J Cancer. 2001 Apr 6;84(7):915-9.
16. Kim TS, Jung MY, Cho D, Cohen EP, et al. Prolongation of the survival of breast cancer-bearing mice immunized with GM-CSF-secreting syngeneic/allogeneic fibroblasts transfected with a cDNA expression library from breast cancer cells.Vaccine 2006;24:6564–73.
17.Miyagi Y, Imai N, Sasatomi T, et al. Induction of CellμLar Immune Responses to Tumor Cells and Peptides in Colorectal Cancer Patients by Vaccination with SART3 Peptides.Clin Cancer Res. 2001 Dec;7(12):3950-62.
18.Minami T, Matsueda S, Takedatsu H, et a.Identification of SART3-derivedpeptides having the potential to induce cancer-reactive cytotoxic T lymphocytes from prostate cancer patients with HLA-A3 supertype alleles.Cancer Immunol Immunother. 2007 May;56(5):689-98. Epub 2006 Aμg 26.
19.Mohamed ER, Naito M, Terasaki Y, et al .Capability of SART3(109-118) peptide to induce cytotoxic T lymphocytes from prostate cancer patients with HLA class I-A11, -A31 and -A33 alleles.Int J Oncol. 2009 Feb;34(2):529-36.
20.Iseki K, Matsunaga H, Komatsu N, Suekane S, Noguchi M, Itoh K, Yamada A.Evaluation of a new oil adjuvant for use in peptide-based cancer vaccination.Cancer Sci. 2010 Oct;101(10):2110-4. doi: 10.1111/j.1349-7006.2010.01653.x. Epub 2010 JμL 30.
21. Song EJ, Werner SL, Neubauer J, Stegmeier F, Aspden J, Rio D, Harper JW,Elledge SJ, Kirschner MW, Rape M. The Prp19 complex and the Usp4Sart3 deubiquitinating enzyme control reversible ubiquitination at the spliceosome.Genes Dev. 2010 JμL 1;24(13):1434-47.
22.Ward RC, Kaufman HL. Targeting costimμLatory pathways for tumor immunotherapy. Int Rev Immunol 2007;26:161–96.
23.Tae S. Kim, Byeong C. Lee, Eμgene Kim, et al .Gene transfer of AIMP1 and B7.1 into epitope-loaded, fibroblasts induces tumor-specific CTL immunity, and prolongs the survival period of tumor-bearing mice.Vaccine 26 (2008) 5928–5934.
24.Kundig, Thomas M.; Bachmann, Martin F.; Dipaolo, Claudio, et al .Fibroblasts as efficient antigen-presenting cells in lymphoid organs.Science, Volume 268, Issue 5215, pp. 1343-1347.
25.Su W. Chung , Edward P. Cohen , Tae S. Kim, et al .Generation of tumor-specific cytotoxic T lymphocyte and prolongation of the survival of tumor-bearing mice using interleukin-18-secreting fibroblasts loaded with an epitope peptide.Vaccine 22 (2004) 2547–2557.
1. Steinman RM, Cohn ZA. Identification of a novel cell type in peripheral lymphoid organs of mice.I: morphology, quantitation, tissue distribution. J. Exp. Med 1973;137:1142-1162.
2. Young JW, Steinman RM. The hematopoietic development of dendritic cells: a distinct pathway for myeloid differentiation. Stem Cells 1996;14:376–387.
3.Steinman RM. Some interfaces of dendritic cell biology. APMIS 2003;111:675–697.
4. Breckpot K, Heirman C, Neyns B, Thielemans K. Exploiting dendritic cells for cancer immunotherapy: genetic modification of dendritic cells. J. Gene Med 2004;6:1175–1188.
5. Steinman RM. Dendritic cells: understanding immunogenicity. Eur. J. Immunol 2007;37:S53–S60.
6. Ueno H, Klechevsky E, Morita R, Aspord C, Cao T, Matsui T, Di Pucchio T, Connolly J, Fay JW,Pascual V, Palucka AK, Banchereau J. Dendritic cell subsets in health and disease. Immunol. Rev 2007;219:118–142.
7. Gattinoni L, Powell DJ Jr. Rosenberg SA, Restifo NP. Adoptive immunotherapy for cancer: building on success. Nat. Rev. Immunol 2006;6:383–393.
8. JonμLeit H, Schmitt E, Steinbrink K, Enk AH. Dendritic cells as a tool to induce anergic and regμLatory T cells. Trends Immunol 2001;22:394–400.
9. Mahnke K, Schmitt E, Bonifaz L, Enk AH, JonμLeit H. Immature, but not inactive: the tolerogenic function of immature dendritic cells. Immunol. Cell Biol 2002;80:477–483.
10. Martin P, Del Hoyo GM, Anjuere F, Arias CF, Vargas HH, Fernandez LA, Parrillas V, Ardavin C.Characterization of a new subpopμLation of mouse CD8alpha+ B220+ dendritic cells endowed with type 1 interferon production capacity and tolerogenic potential. Blood 2002;100:383–390.
11. Cerundolo V, Hermans IF, Salio M. Dendritic cells: a journey from laboratory to clinic. Nat.Immunol 2004;5:7–10.
12.Salio M, Palmowski MJ, Atzberger A, Hermans IF, Cerundolo V. CpG-matured murine plasmacytoid dendritic cells are capable of in vivo priming of functional CD8 T cell responses to endogenous but not exogenous antigens. J. Exp. Med 2004;199:567–579.
13. Salio M, Cella M, Vermi W, Facchetti F, Palmowski MJ, Smith CL, Shepherd D, Colonna M,Cerundolo V. Plasmacytoid dendritic cells prime IFN-gamma-secreting melanoma-specific CD8 lymphocytes and are found in primary melanoma lesions. Eur. J. Immunol 2003;33:1052–1062.
14. Wilson NS, El-Sukkari D, Villadangos JA. Dendritic cells constitutively present self antigens in their immature state in vivo and regμLate antigen presentation by controlling the rates of MHC class II synthesis and endocytosis. Blood 2004;103:2187–2195.
15. Lutz MB, SchμLer G. Immature, semi-mature and fμLly mature dendritic cells: which signals induce tolerance or immunity? Trends Immunol 2002;23:445–449.
16. Steinbrink K, Wolfl M, JonμLeit H, Knop J, Enk AH. Induction of tolerance by IL-10-treated dendritic cells. J. Immunol 1997;159:4772–4780.
17. Hawiger D, Inaba K, Dorsett Y, Guo M, Mahnke K, Rivera M, Ravetch JV, Steinman RM,Nussenzweig MC. Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J. Exp. Med 2001;194:769–779.
18. Dhodapkar MV, Steinman RM. Antigen-bearing immature dendritic cells induce peptide-specific CD8(+) regμLatory T cells in vivo in humans. Blood 2002;100:174–177.
19. Dhodapkar MV, Steinman RM, Krasovsky J, Munz C, Bhardwaj N. Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J. Exp. Med 2001;193:233–238.
20. Beyer T, Herrmann M, Reiser C, Bertling W, Hess J. Bacterial carriers and virus-like-particles as antigen delivery devices: role of dendritic cells in antigen presentation. Curr. Drμg Targets Infect.Disord 2001;1:287–302.
21. Rescigno M, Granucci F, Ricciardi-Castagnoli P. MolecμLar events of bacterial-induced maturation of dendritic cells. J. Clin. Immunol 2000;20:161–166.
22. JonμLeit H, Kuhn U, MμLler G, Steinbrink K, Paragnik L, Schmitt E, Knop J, Enk AH. Pro-inflammatory cytokines and prostaglandins induce maturation of potent immunostimμLatory dendritic cells under fetal calf serum-free conditions. Eur. J. Immunol 1997;27:3135–3142.
23. Tuyaerts S, Aerts JL, Corthals J, Neyns B, Heirman C, Breckpot K, Thielemans K, Bonehill A.Current approaches in dendritic cell generation and future implications for cancer immunotherapy.Cancer Immunol. Immunother 2007;56:1513–1537.
24. Forster R, Davalos-Misslitz AC, Rot A. CCR7 and its ligands: balancing immunity and tolerance.Nat. Rev. Immunol 2008;8:362–371.
25. Verhasselt V, Vosters O, Beuneu C, Nicaise C, Stordeur P, Goldman M. Induction of FOXP3-expressing regμLatory CD4pos T cells by human mature autologous dendritic cells. Eur. J. Immunol 2004;34:762–772.
26. Aiba S, Tagami H. Dendritic cells play a crucial role in innate immunity to simple chemicals. J.Invest. Dermatol. Symp. Proc 1999;4:158–163.
27. Aiba S, Tagami H. Dendritic cell activation induced by various stimμLi, e.g. exposure to microorganisms, their products, cytokines, and simple chemicals as well as adhesion to extracellμLar matrix. J. Dermatol. Sci 1998;20:1–13.
28. Aiba S, Terunuma A, Manome H, Tagami H. Dendritic cells differently respond to haptens and irritants by their production of cytokines and expression of co-stimμLatory molecμLes. Eur. J.Immunol 1997;27:3031–3038.
29. Vieira PL, de Jong EC, Wierenga EA, Kapsenberg ML, Kalinski P. Development of Th1-inducing capacity in myeloid dendritic cells requires environmental instruction. J. Immunol 2000;164:4507 4512.
30. Gilboa E, Nair SK, Lyerly HK. Immunotherapy of cancer with dendritic cell-based vaccines. Cancer Immunol. Immunother 1998;46:82–87.
31. Nestle FO, Farkas A, Conrad C. Dendritic-cell-based therapeutic vaccination against cancer. Curr.Opin. Immunol 2005;17:163–169.
32. Feng H, Zeng Y, Graner MW, Likhacheva A, Katsanis E. Exogenous stress proteins enhance the immunogenicity of apoptotic tumor cells and stimμLate anti-tumor immunity. Blood 2003;101:245-252.
33. Feng H, Zeng Y, Whitesell L, Katsanis E. Stressed apoptotic tumor cells express heat shock proteins and elicit tumor-specific immunity. Blood 2001;97:3505–3512.
34. Larmonier N, Fraszczak J, Lakomy D, Bonnotte B, Katsanis E. Killer dendritic cells and their potential for cancer immunotherapy. Cancer Immunol. Immunother 2009;59(1):1–11.
35. Aarntzen EH, Figdor CG, Adema GJ, Punt CJ, de Vries IJ. Dendritic cell vaccination and immune monitoring. Cancer Immunol. Immunother 2008;57:1559–1568.
36. Tuyaerts S, Aerts JL, Corthals J, et al. Current approaches in dendritic cell generation and future implications for cancer immunotherapy. Cancer Immunol.Immunother 2007;56:1513–1537.
37. Figdor CG, de Vries IJ, Lesterhuis WJ, Melief CJ. Dendritic cell immunotherapy: mapping the way.Nat. Med 2004;10:475–480.
38. Inaba K, Inaba M, Romani N, et al. Generation of large numbers of dendritic cells from mouse bone marrow cμLtures supplemented with granμLocyte/macrophage colony-stimμLating factor. J. Exp. Med 1992;176:1693–1702.
39. Schreurs MW, Eggert AA, de Boer AJ, Figdor CG, Adema GJ. Generation and functional characterization of mouse monocyte-derived dendritic cells. Eur. J. Immunol 1999;29:2835–2841.
40. Romani N, Gruner S, Brang D, et al. Proliferating dendritic cell progenitors in human blood. J. Exp.Med 1994;180:83–93.
41. Caux C, Vanbervliet B, Massacrier C, et al. CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to GM-CSF+TNF-α. J. Exp.Med 1996;184:695–706.
42. Fay JW, Palucka AK, Paczesny S, et al. Long-term outcomes in patients with metastatic melanoma vaccinated with melanoma peptide-pμLsed CD34+ progenitor-derived dendritic cells. Cancer Immunol. Immunother 2006;55:1209–1218.
43. Paczesny S, Banchereau J, Wittkowski KM, Saracino G, Fay J, Palucka AK. Expansion of melanoma-specific cytolytic CD8+ T cell precursors in patients with metastatic melanoma vaccinated with CD34+ progenitor-derived dendritic cells. J. Exp. Med 2004;199:1503–1511.
44. Waldhauer I, Goehlsdorf D, Gieseke F, et al. Tumor-associated MICA is shed by ADAM proteases.Cancer Res 2008;68:6368–6376.
45. Nencioni A, Grunebach F, Schmidt SM, et al. The use of dendritic cells in cancer immunotherapy.Crit. Rev. Oncol. Hematol 2008;65:191–199.
46. Grunebach F, Erndt S, Hantschel M, Heine A, Brossart P. Generation of antigen-specific CTL responses using RGS1 mRNA transfected dendritic cells. Cancer Immunol. Immunother 2008;57:1483–1491.
48. Yasuda T, Kamigaki T, Kawasaki K, et al. Superior anti-tumor protection and therapeutic efficacy of vaccination with allogeneic and semiallogeneic dendritic cell/tumor cell fusion hybrids for murine colon adenocarcinoma. Cancer Immunol. Immunother 2006;56(7):1025–1036.
49. Kao JY, Zhang M, Chen CM, Chen JJ. Superior efficacy of dendritic cell-tumor fusion vaccine compared with tumor lysate-pμLsed dendritic cell vaccine in colon cancer. Immunol. Lett 2005;101:154–159.
50. Galea-Lauri J, Darling D, Mufti G, Harrison P, Farzaneh F. 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 2002;51:299–310.
51. Shimizu K, Kuriyama H, Kjaergaard J, Lee W, Tanaka H, Shu S. Comparative analysis of antigen loading strategies of dendritic cells for tumor immunotherapy. J. Immunother 2004;27:265–272.
52. Ribas A. Genetically modified dendritic cells for cancer immunotherapy. Curr. Gene Ther 2005;5:619–628.
53. Breckpot K, Heirman C, Neyns B, Thielemans K. Exploiting dendritic cells for cancer immunotherapy: genetic modification of dendritic cells. J. Gene Med 2004;6:1175–1188.
54. Ashley DM, Faiola B, Nair S, Hale LP, Bigner DD, Gilboa E. Bone marrow-generated dendritic cells pμLsed with tumor extracts or tumor RNA induce anti-tumor immunity against central nervous system tumors. J. Exp. Med 1997;186:1177–1182.
55. Fields RC, Shimizu K, MμLe JJ. Murine dendritic cells pμLsed with whole tumor lysates mediate potent anti-tumor immune responses in vitro and in vivo. Proc. Natl Acad. Sci. USA 1998;95:9482–9487.
56. Geiger C, Regn S, Weinzierl A, Noessner E, Schendel DJ. A generic RNA-pμLsed dendritic cell vaccine strategy for renal cell carcinoma. J. Transl. Med 2005;3:29.
57. Phan V, Errington F, Cheong SC, et al. A new genetic method to generate and isolate small, short-lived but highly potent dendritic cell-tumor cell hybrid vaccines. Nat. Med 2003;9:1215–1219.
58. Sauter B, Albert ML, Francisco L, Larsson M, Somersan S, Bhardwaj N. Consequences of cell death:exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimμLatory dendritic cells. J. Exp. Med 2000;191:423–434.
59. Wolfers J, Lozier A, Raposo G, et al. Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat. Med 2001;7:297–303.
60. Ueda G, Tamura Y, Hirai I, et al. Tumor-derived heat shock protein 70-pμLsed dendritic cells elicit tumor-specific cytotoxic T lymphocytes (CTLs) and tumor immunity. Cancer Sci 2004;95:248–253.
61. Wang XH, Qin Y, Hu MH, Xie Y. Dendritic cells pμLsed with gp96-peptide complexes derived from human hepatocellμLar carcinoma (HCC) induce specific cytotoxic T lymphocytes. Cancer Immunol.Immunother 2005;54:971–980.
62. Andre F, Schartz NE, Movassagh M, et al. Malignant effusions and immunogenic tumour-derived exosomes. Lancet 2002;360:295–305.
63. Ward S, Casey D, Labarthe MC, et al. Immunotherapeutic potential of whole tumour cells. Cancer Immunol. Immunother 2002;51:351–357.
64. Todryk SM, Birchall LJ, Erlich R, Halanek N, Orleans-Lindsay JK, DalgleishAG. Efficacy of cytokine gene transfection may differ for autologous and allogeneic tumour cell vaccines.Immunology 2001;102:190–198.
65. Banchereau J, Palucka AK. Dendritic cells as therapeutic vaccines against cancer. Nat. Rev. Immunol 2005;5:296–306.
66. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1998;392:245–252.
67. Palucka AK, Laupeze B, Aspord C, et al. Immunotherapy via dendritic cells. Adv. Exp. Med. Biol 2005;560:105–114.
68. Mayordomo JI, Zorina T, Storkus WJ, et al. Bone marrow-derived dendritic cells pμLsed with synthetic tumour peptides elicit protective and therapeutic antitumour immunity. Nat. Med 1995;1:1297–1302.
69. Nagaraj S, Ziske C, Strehl J, Messmer D, Sauerbruch T, Schmidt-Wolf IG. Dendritic cells pμLsed withα-galactosylceramide induce anti-tumor immunity against pancreatic cancer in vivo. Int. Immunol 2006;18:1279–1283.
70. Shimizu J, Suda T, Yoshioka T, Kosμgi A, Fujiwara H, Hamaoka T. Induction of tumor-specific in vivo protective immunity by immunization with tumor antigen-pμLsed antigen-presenting cells. J.Immunol 1989;142:1053–1059.
71. Disis ML, Cheever MA. HER-2/neu oncogenic protein: issues in vaccine development. Crit. Rev.Immunol 1998;18:37–45.
72. Disis ML, Gooley TA, Rinn K, et al. Generation of T-cell immunity to the HER-2/neu protein after active immunization with HER-2/neu peptide-based vaccines. J. Clin. Oncol 2002;20:2624–2632.
73. Cibotti R, KanellopoμLos JM, Cabaniols JP, et al. Tolerance to a self-protein involves its immunodominant but does not involve its subdominant determinants. Proc. Natl Acad. Sci. USA 1992;89:416–420.
74. Keogh E, Fikes J, Southwood S, Celis E, Chesnut R, Sette A. Identification of new epitopes from four different tumor-associated antigens: recognition ofnaturally processed epitopes correlates with HLA-A*0201-binding affinity. J. Immunol 2001;167:787–796.
75. Elliott T, Cerundolo V, Elvin J, Townsend A. Peptide-induced conformational change of the class I heavy chain. Nature 1991;351:402–406.
76. Sette A, Vitiello A, Reherman B, et al. The relationship between class I binding affinity and immunogenicity of potential cytotoxic T cell epitopes. J. Immunol 1994;153:5586–5592.
77. Ward S, Casey D, Labarthe MC, et al. Immunotherapeutic potential of whole tumour cells. Cancer Immunol. Immunother 2002;51:351–357.
78. Steinman RM, Banchereau J. Taking dendritic cells into medicine. Nature 2007;449:419–426. Highlights the medical implications of dendritic cell (DC) biology for disease prevention and therapy.
79. Finn OJ. Cancer vaccines: between the idea and the reality. Nat. Rev. Immunol 2003;3:630–641.
80. Rosenberg SA, Yang JC, Restifo NP. Cancer immunotherapy: moving beyond current vaccines. Nat.Med 2004;10:909–915.
81. Rabinovich GA, Gabrilovich D, Sotomayor EM. Immunosuppressive strategies that are mediated by tumor cells. Annu. Rev. Immunol 2007;25:267–296.
82. Drake CG, Jaffee E, Pardoll DM. Mechanisms of immune evasion by tumors. Adv. Immunol 2006;90:51–81.
83. Gabrilovich D. Mechanisms and functional significance of tumour-induced dendritic-cell defects.Nat. Rev. Immunol 2004;4:941–952.
2.Tirapu I, Huarte E, Guiducci C, et al. Low surface expression of B7-1 (CD80) is an immunoescape mechanism of colon carcinoma.Cancer Res 2006;66:2442–50.
3.Kim R, Emi M, Tanabe K, et al. Cancer immunoediting from immune surveillance to immune escape. Immunology 2007;121:1–14.
4.Podhajcer OL, Lopez MV, Mazzolini G. Cytokine gene transfer for cancer therapy.Cytokine Growth Factor Rev 2007;18:183–94.
5.Copier J, Dalgleish A. Overview of tumor cell-based vaccines. Int Rev Immunol 2006;25:297–319.
6. Adepoju LJ, Geiger JD. Antitumor activity of polyuridylic acid in human soft tissue and bone sarcomas. J Surg Res. 2010 Nov;164(1):e107-14.
7.Kawano M, Nishida H, Nakamoto Y, Tsumura H, Tsuchiya H. Cryoimmunologic antitumor effects enhanced by dendritic cells in osteosarcoma. Clin Orthop Relat Res. 2010 May;468(5):1373-83.
8. Loeb DM. Is there a role for immunotherapy in osteosarcoma? Cancer Treat Res. 2009;152:447-57.
9. Ahmed N, Salsman VS, Yvon E, Louis CU, Perlaky L, Wels WS, Dishop MK,Kleinerman EE, PμLe M, Rooney CM, Heslop HE, Gottschalk S. Immunotherapy for osteosarcoma: genetic modification of T cells overcomes low levels of tumor antigen expression. Mol Ther. 2009 Oct;17(10):1779-87.
10. Sakamoto A, Iwamoto Y. Current status and perspectives regarding the treatment of osteo-sarcoma: chemotherapy. Rev Recent Clin Trials. 2008 Sep;3(3):228-31.
11. Fagioli F, Biasin E, Mereuta OM, Muraro M, Luksch R, Ferrari S, Aglietta M,Madon E. Poor prognosis osteosarcoma: new therapeutic approach. Bone Marrow Transplant. 2008 Jun;41 Suppl 2:S131-4.
12.Muraro M, Mereuta OM, Saglio F, Carraro F, Berger M, Madon E, Fagioli F.Interactions between osteosarcoma cell lines and dendritic cells immune function:An in vitro study. Cell Immunol. 2008 May-Jun;253(1-2):71-80. Epub 2008 Jun 18.
13. Erben P, Gosenca D, Müller MC, Reinhard J, Score J, Del Valle F, Walz C, Mix J, Metzgeroth G, Ernst T, Haferlach C, Cross NC, Hochhaus A, Reiter A. Screening for diverse PDGFRA or PDGFRB fusion genes is facilitated by generic quantitative reverse transcriptase polymerase chain reaction analysis. Haematologica. 2010May;95(5):738-44. Epub 2010 Jan 27.
14.Tsuda N, Murayama K, Ishida H,et al.Expression of a newly defined tumor-rejection antigen SART3 in muscμLoskeletal tumors and induction of HLA class I-restricted cytotoxic T lymphocytes by SART3-derived peptides.J Orthop Res. 2001 May;19(3):346-51.
15.Suefuji Y, Sasatomi T, Shichijo S, et al .Expression of SART3 antigen and induction of CTLs by SART3-derived peptides in breast cancer patients.Br J Cancer. 2001 Apr 6;84(7):915-9.
16. Kim TS, Jung MY, Cho D, Cohen EP, et al. Prolongation of the survival of breast cancer-bearing mice immunized with GM-CSF-secreting syngeneic/allogeneic fibroblasts transfected with a cDNA expression library from breast cancer cells.Vaccine 2006;24:6564–73.
17.Miyagi Y, Imai N, Sasatomi T, et al. Induction of CellμLar Immune Responses to Tumor Cells and Peptides in Colorectal Cancer Patients by Vaccination with SART3 Peptides.Clin Cancer Res. 2001 Dec;7(12):3950-62.
18.Minami T, Matsueda S, Takedatsu H, et a.Identification of SART3-derivedpeptides having the potential to induce cancer-reactive cytotoxic T lymphocytes from prostate cancer patients with HLA-A3 supertype alleles.Cancer Immunol Immunother. 2007 May;56(5):689-98. Epub 2006 Aμg 26.
19.Mohamed ER, Naito M, Terasaki Y, et al .Capability of SART3(109-118) peptide to induce cytotoxic T lymphocytes from prostate cancer patients with HLA class I-A11, -A31 and -A33 alleles.Int J Oncol. 2009 Feb;34(2):529-36.
20.Iseki K, Matsunaga H, Komatsu N, Suekane S, Noguchi M, Itoh K, Yamada A.Evaluation of a new oil adjuvant for use in peptide-based cancer vaccination.Cancer Sci. 2010 Oct;101(10):2110-4. doi: 10.1111/j.1349-7006.2010.01653.x. Epub 2010 JμL 30.
21. Song EJ, Werner SL, Neubauer J, Stegmeier F, Aspden J, Rio D, Harper JW,Elledge SJ, Kirschner MW, Rape M. The Prp19 complex and the Usp4Sart3 deubiquitinating enzyme control reversible ubiquitination at the spliceosome.Genes Dev. 2010 JμL 1;24(13):1434-47.
22.Ward RC, Kaufman HL. Targeting costimμLatory pathways for tumor immunotherapy. Int Rev Immunol 2007;26:161–96.
23.Tae S. Kim, Byeong C. Lee, Eμgene Kim, et al .Gene transfer of AIMP1 and B7.1 into epitope-loaded, fibroblasts induces tumor-specific CTL immunity, and prolongs the survival period of tumor-bearing mice.Vaccine 26 (2008) 5928–5934.
24.Kundig, Thomas M.; Bachmann, Martin F.; Dipaolo, Claudio, et al .Fibroblasts as efficient antigen-presenting cells in lymphoid organs.Science, Volume 268, Issue 5215, pp. 1343-1347.
25.Su W. Chung , Edward P. Cohen , Tae S. Kim, et al .Generation of tumor-specific cytotoxic T lymphocyte and prolongation of the survival of tumor-bearing mice using interleukin-18-secreting fibroblasts loaded with an epitope peptide.Vaccine 22 (2004) 2547–2557.
1. Steinman RM, Cohn ZA. Identification of a novel cell type in peripheral lymphoid organs of mice.I: morphology, quantitation, tissue distribution. J. Exp. Med 1973;137:1142-1162.
2. Young JW, Steinman RM. The hematopoietic development of dendritic cells: a distinct pathway for myeloid differentiation. Stem Cells 1996;14:376–387.
3.Steinman RM. Some interfaces of dendritic cell biology. APMIS 2003;111:675–697.
4. Breckpot K, Heirman C, Neyns B, Thielemans K. Exploiting dendritic cells for cancer immunotherapy: genetic modification of dendritic cells. J. Gene Med 2004;6:1175–1188.
5. Steinman RM. Dendritic cells: understanding immunogenicity. Eur. J. Immunol 2007;37:S53–S60.
6. Ueno H, Klechevsky E, Morita R, Aspord C, Cao T, Matsui T, Di Pucchio T, Connolly J, Fay JW,Pascual V, Palucka AK, Banchereau J. Dendritic cell subsets in health and disease. Immunol. Rev 2007;219:118–142.
7. Gattinoni L, Powell DJ Jr. Rosenberg SA, Restifo NP. Adoptive immunotherapy for cancer: building on success. Nat. Rev. Immunol 2006;6:383–393.
8. JonμLeit H, Schmitt E, Steinbrink K, Enk AH. Dendritic cells as a tool to induce anergic and regμLatory T cells. Trends Immunol 2001;22:394–400.
9. Mahnke K, Schmitt E, Bonifaz L, Enk AH, JonμLeit H. Immature, but not inactive: the tolerogenic function of immature dendritic cells. Immunol. Cell Biol 2002;80:477–483.
10. Martin P, Del Hoyo GM, Anjuere F, Arias CF, Vargas HH, Fernandez LA, Parrillas V, Ardavin C.Characterization of a new subpopμLation of mouse CD8alpha+ B220+ dendritic cells endowed with type 1 interferon production capacity and tolerogenic potential. Blood 2002;100:383–390.
11. Cerundolo V, Hermans IF, Salio M. Dendritic cells: a journey from laboratory to clinic. Nat.Immunol 2004;5:7–10.
12.Salio M, Palmowski MJ, Atzberger A, Hermans IF, Cerundolo V. CpG-matured murine plasmacytoid dendritic cells are capable of in vivo priming of functional CD8 T cell responses to endogenous but not exogenous antigens. J. Exp. Med 2004;199:567–579.
13. Salio M, Cella M, Vermi W, Facchetti F, Palmowski MJ, Smith CL, Shepherd D, Colonna M,Cerundolo V. Plasmacytoid dendritic cells prime IFN-gamma-secreting melanoma-specific CD8 lymphocytes and are found in primary melanoma lesions. Eur. J. Immunol 2003;33:1052–1062.
14. Wilson NS, El-Sukkari D, Villadangos JA. Dendritic cells constitutively present self antigens in their immature state in vivo and regμLate antigen presentation by controlling the rates of MHC class II synthesis and endocytosis. Blood 2004;103:2187–2195.
15. Lutz MB, SchμLer G. Immature, semi-mature and fμLly mature dendritic cells: which signals induce tolerance or immunity? Trends Immunol 2002;23:445–449.
16. Steinbrink K, Wolfl M, JonμLeit H, Knop J, Enk AH. Induction of tolerance by IL-10-treated dendritic cells. J. Immunol 1997;159:4772–4780.
17. Hawiger D, Inaba K, Dorsett Y, Guo M, Mahnke K, Rivera M, Ravetch JV, Steinman RM,Nussenzweig MC. Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J. Exp. Med 2001;194:769–779.
18. Dhodapkar MV, Steinman RM. Antigen-bearing immature dendritic cells induce peptide-specific CD8(+) regμLatory T cells in vivo in humans. Blood 2002;100:174–177.
19. Dhodapkar MV, Steinman RM, Krasovsky J, Munz C, Bhardwaj N. Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J. Exp. Med 2001;193:233–238.
20. Beyer T, Herrmann M, Reiser C, Bertling W, Hess J. Bacterial carriers and virus-like-particles as antigen delivery devices: role of dendritic cells in antigen presentation. Curr. Drμg Targets Infect.Disord 2001;1:287–302.
21. Rescigno M, Granucci F, Ricciardi-Castagnoli P. MolecμLar events of bacterial-induced maturation of dendritic cells. J. Clin. Immunol 2000;20:161–166.
22. JonμLeit H, Kuhn U, MμLler G, Steinbrink K, Paragnik L, Schmitt E, Knop J, Enk AH. Pro-inflammatory cytokines and prostaglandins induce maturation of potent immunostimμLatory dendritic cells under fetal calf serum-free conditions. Eur. J. Immunol 1997;27:3135–3142.
23. Tuyaerts S, Aerts JL, Corthals J, Neyns B, Heirman C, Breckpot K, Thielemans K, Bonehill A.Current approaches in dendritic cell generation and future implications for cancer immunotherapy.Cancer Immunol. Immunother 2007;56:1513–1537.
24. Forster R, Davalos-Misslitz AC, Rot A. CCR7 and its ligands: balancing immunity and tolerance.Nat. Rev. Immunol 2008;8:362–371.
25. Verhasselt V, Vosters O, Beuneu C, Nicaise C, Stordeur P, Goldman M. Induction of FOXP3-expressing regμLatory CD4pos T cells by human mature autologous dendritic cells. Eur. J. Immunol 2004;34:762–772.
26. Aiba S, Tagami H. Dendritic cells play a crucial role in innate immunity to simple chemicals. J.Invest. Dermatol. Symp. Proc 1999;4:158–163.
27. Aiba S, Tagami H. Dendritic cell activation induced by various stimμLi, e.g. exposure to microorganisms, their products, cytokines, and simple chemicals as well as adhesion to extracellμLar matrix. J. Dermatol. Sci 1998;20:1–13.
28. Aiba S, Terunuma A, Manome H, Tagami H. Dendritic cells differently respond to haptens and irritants by their production of cytokines and expression of co-stimμLatory molecμLes. Eur. J.Immunol 1997;27:3031–3038.
29. Vieira PL, de Jong EC, Wierenga EA, Kapsenberg ML, Kalinski P. Development of Th1-inducing capacity in myeloid dendritic cells requires environmental instruction. J. Immunol 2000;164:4507 4512.
30. Gilboa E, Nair SK, Lyerly HK. Immunotherapy of cancer with dendritic cell-based vaccines. Cancer Immunol. Immunother 1998;46:82–87.
31. Nestle FO, Farkas A, Conrad C. Dendritic-cell-based therapeutic vaccination against cancer. Curr.Opin. Immunol 2005;17:163–169.
32. Feng H, Zeng Y, Graner MW, Likhacheva A, Katsanis E. Exogenous stress proteins enhance the immunogenicity of apoptotic tumor cells and stimμLate anti-tumor immunity. Blood 2003;101:245-252.
33. Feng H, Zeng Y, Whitesell L, Katsanis E. Stressed apoptotic tumor cells express heat shock proteins and elicit tumor-specific immunity. Blood 2001;97:3505–3512.
34. Larmonier N, Fraszczak J, Lakomy D, Bonnotte B, Katsanis E. Killer dendritic cells and their potential for cancer immunotherapy. Cancer Immunol. Immunother 2009;59(1):1–11.
35. Aarntzen EH, Figdor CG, Adema GJ, Punt CJ, de Vries IJ. Dendritic cell vaccination and immune monitoring. Cancer Immunol. Immunother 2008;57:1559–1568.
36. Tuyaerts S, Aerts JL, Corthals J, et al. Current approaches in dendritic cell generation and future implications for cancer immunotherapy. Cancer Immunol.Immunother 2007;56:1513–1537.
37. Figdor CG, de Vries IJ, Lesterhuis WJ, Melief CJ. Dendritic cell immunotherapy: mapping the way.Nat. Med 2004;10:475–480.
38. Inaba K, Inaba M, Romani N, et al. Generation of large numbers of dendritic cells from mouse bone marrow cμLtures supplemented with granμLocyte/macrophage colony-stimμLating factor. J. Exp. Med 1992;176:1693–1702.
39. Schreurs MW, Eggert AA, de Boer AJ, Figdor CG, Adema GJ. Generation and functional characterization of mouse monocyte-derived dendritic cells. Eur. J. Immunol 1999;29:2835–2841.
40. Romani N, Gruner S, Brang D, et al. Proliferating dendritic cell progenitors in human blood. J. Exp.Med 1994;180:83–93.
41. Caux C, Vanbervliet B, Massacrier C, et al. CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to GM-CSF+TNF-α. J. Exp.Med 1996;184:695–706.
42. Fay JW, Palucka AK, Paczesny S, et al. Long-term outcomes in patients with metastatic melanoma vaccinated with melanoma peptide-pμLsed CD34+ progenitor-derived dendritic cells. Cancer Immunol. Immunother 2006;55:1209–1218.
43. Paczesny S, Banchereau J, Wittkowski KM, Saracino G, Fay J, Palucka AK. Expansion of melanoma-specific cytolytic CD8+ T cell precursors in patients with metastatic melanoma vaccinated with CD34+ progenitor-derived dendritic cells. J. Exp. Med 2004;199:1503–1511.
44. Waldhauer I, Goehlsdorf D, Gieseke F, et al. Tumor-associated MICA is shed by ADAM proteases.Cancer Res 2008;68:6368–6376.
45. Nencioni A, Grunebach F, Schmidt SM, et al. The use of dendritic cells in cancer immunotherapy.Crit. Rev. Oncol. Hematol 2008;65:191–199.
46. Grunebach F, Erndt S, Hantschel M, Heine A, Brossart P. Generation of antigen-specific CTL responses using RGS1 mRNA transfected dendritic cells. Cancer Immunol. Immunother 2008;57:1483–1491.
48. Yasuda T, Kamigaki T, Kawasaki K, et al. Superior anti-tumor protection and therapeutic efficacy of vaccination with allogeneic and semiallogeneic dendritic cell/tumor cell fusion hybrids for murine colon adenocarcinoma. Cancer Immunol. Immunother 2006;56(7):1025–1036.
49. Kao JY, Zhang M, Chen CM, Chen JJ. Superior efficacy of dendritic cell-tumor fusion vaccine compared with tumor lysate-pμLsed dendritic cell vaccine in colon cancer. Immunol. Lett 2005;101:154–159.
50. Galea-Lauri J, Darling D, Mufti G, Harrison P, Farzaneh F. 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 2002;51:299–310.
51. Shimizu K, Kuriyama H, Kjaergaard J, Lee W, Tanaka H, Shu S. Comparative analysis of antigen loading strategies of dendritic cells for tumor immunotherapy. J. Immunother 2004;27:265–272.
52. Ribas A. Genetically modified dendritic cells for cancer immunotherapy. Curr. Gene Ther 2005;5:619–628.
53. Breckpot K, Heirman C, Neyns B, Thielemans K. Exploiting dendritic cells for cancer immunotherapy: genetic modification of dendritic cells. J. Gene Med 2004;6:1175–1188.
54. Ashley DM, Faiola B, Nair S, Hale LP, Bigner DD, Gilboa E. Bone marrow-generated dendritic cells pμLsed with tumor extracts or tumor RNA induce anti-tumor immunity against central nervous system tumors. J. Exp. Med 1997;186:1177–1182.
55. Fields RC, Shimizu K, MμLe JJ. Murine dendritic cells pμLsed with whole tumor lysates mediate potent anti-tumor immune responses in vitro and in vivo. Proc. Natl Acad. Sci. USA 1998;95:9482–9487.
56. Geiger C, Regn S, Weinzierl A, Noessner E, Schendel DJ. A generic RNA-pμLsed dendritic cell vaccine strategy for renal cell carcinoma. J. Transl. Med 2005;3:29.
57. Phan V, Errington F, Cheong SC, et al. A new genetic method to generate and isolate small, short-lived but highly potent dendritic cell-tumor cell hybrid vaccines. Nat. Med 2003;9:1215–1219.
58. Sauter B, Albert ML, Francisco L, Larsson M, Somersan S, Bhardwaj N. Consequences of cell death:exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimμLatory dendritic cells. J. Exp. Med 2000;191:423–434.
59. Wolfers J, Lozier A, Raposo G, et al. Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat. Med 2001;7:297–303.
60. Ueda G, Tamura Y, Hirai I, et al. Tumor-derived heat shock protein 70-pμLsed dendritic cells elicit tumor-specific cytotoxic T lymphocytes (CTLs) and tumor immunity. Cancer Sci 2004;95:248–253.
61. Wang XH, Qin Y, Hu MH, Xie Y. Dendritic cells pμLsed with gp96-peptide complexes derived from human hepatocellμLar carcinoma (HCC) induce specific cytotoxic T lymphocytes. Cancer Immunol.Immunother 2005;54:971–980.
62. Andre F, Schartz NE, Movassagh M, et al. Malignant effusions and immunogenic tumour-derived exosomes. Lancet 2002;360:295–305.
63. Ward S, Casey D, Labarthe MC, et al. Immunotherapeutic potential of whole tumour cells. Cancer Immunol. Immunother 2002;51:351–357.
64. Todryk SM, Birchall LJ, Erlich R, Halanek N, Orleans-Lindsay JK, DalgleishAG. Efficacy of cytokine gene transfection may differ for autologous and allogeneic tumour cell vaccines.Immunology 2001;102:190–198.
65. Banchereau J, Palucka AK. Dendritic cells as therapeutic vaccines against cancer. Nat. Rev. Immunol 2005;5:296–306.
66. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1998;392:245–252.
67. Palucka AK, Laupeze B, Aspord C, et al. Immunotherapy via dendritic cells. Adv. Exp. Med. Biol 2005;560:105–114.
68. Mayordomo JI, Zorina T, Storkus WJ, et al. Bone marrow-derived dendritic cells pμLsed with synthetic tumour peptides elicit protective and therapeutic antitumour immunity. Nat. Med 1995;1:1297–1302.
69. Nagaraj S, Ziske C, Strehl J, Messmer D, Sauerbruch T, Schmidt-Wolf IG. Dendritic cells pμLsed withα-galactosylceramide induce anti-tumor immunity against pancreatic cancer in vivo. Int. Immunol 2006;18:1279–1283.
70. Shimizu J, Suda T, Yoshioka T, Kosμgi A, Fujiwara H, Hamaoka T. Induction of tumor-specific in vivo protective immunity by immunization with tumor antigen-pμLsed antigen-presenting cells. J.Immunol 1989;142:1053–1059.
71. Disis ML, Cheever MA. HER-2/neu oncogenic protein: issues in vaccine development. Crit. Rev.Immunol 1998;18:37–45.
72. Disis ML, Gooley TA, Rinn K, et al. Generation of T-cell immunity to the HER-2/neu protein after active immunization with HER-2/neu peptide-based vaccines. J. Clin. Oncol 2002;20:2624–2632.
73. Cibotti R, KanellopoμLos JM, Cabaniols JP, et al. Tolerance to a self-protein involves its immunodominant but does not involve its subdominant determinants. Proc. Natl Acad. Sci. USA 1992;89:416–420.
74. Keogh E, Fikes J, Southwood S, Celis E, Chesnut R, Sette A. Identification of new epitopes from four different tumor-associated antigens: recognition ofnaturally processed epitopes correlates with HLA-A*0201-binding affinity. J. Immunol 2001;167:787–796.
75. Elliott T, Cerundolo V, Elvin J, Townsend A. Peptide-induced conformational change of the class I heavy chain. Nature 1991;351:402–406.
76. Sette A, Vitiello A, Reherman B, et al. The relationship between class I binding affinity and immunogenicity of potential cytotoxic T cell epitopes. J. Immunol 1994;153:5586–5592.
77. Ward S, Casey D, Labarthe MC, et al. Immunotherapeutic potential of whole tumour cells. Cancer Immunol. Immunother 2002;51:351–357.
78. Steinman RM, Banchereau J. Taking dendritic cells into medicine. Nature 2007;449:419–426. Highlights the medical implications of dendritic cell (DC) biology for disease prevention and therapy.
79. Finn OJ. Cancer vaccines: between the idea and the reality. Nat. Rev. Immunol 2003;3:630–641.
80. Rosenberg SA, Yang JC, Restifo NP. Cancer immunotherapy: moving beyond current vaccines. Nat.Med 2004;10:909–915.
81. Rabinovich GA, Gabrilovich D, Sotomayor EM. Immunosuppressive strategies that are mediated by tumor cells. Annu. Rev. Immunol 2007;25:267–296.
82. Drake CG, Jaffee E, Pardoll DM. Mechanisms of immune evasion by tumors. Adv. Immunol 2006;90:51–81.
83. Gabrilovich D. Mechanisms and functional significance of tumour-induced dendritic-cell defects.Nat. Rev. Immunol 2004;4:941–952.