Abstract
Effective antitumor immunity requires the generation and persistence of functional tumor-specific T-cell responses. Among the critical factors that often control these responses is how the antigen is delivered and presented to T cells. The use of peptide-based vaccination has been found to be a promising means to induce antitumor T-cell responses but with limited effects even if the peptide is co-delivered with a potent adjuvant. This limited response could be due to cancer-induced dysfunction in dendritic cells (DC), which play a central role in shaping the quantity and quality of antitumor immunity. Therefore, DC-based peptide delivery of tumor antigen is becoming a potential approach in cancer immunotherapy. In this approach, autologous DC are generated from their precursors in bone marrow or peripheral blood mononuclear cells, loaded with tumor antigen(s) and then infused back to the tumor-bearing host in about 7 days. This DC-based vaccination can act as an antigen delivery vehicle as well as a potent adjuvant, resulting in measurable antitumor immunity in several cancer settings in preclinical and clinical studies. This chapter focuses on DC-based vaccination and how this approach can be more efficacious in cancer immunotherapy.
Effective antitumor immunity requires the generation and persistence of functional tumor-specific T-cell responses. Among the critical factors that often control these responses is how the antigen is delivered and presented to T cells. The use of peptide-based vaccination has been found to be a promising means to induce antitumor T-cell responses but with limited effects even if the peptide is co-delivered with a potent adjuvant. This limited response could be due to cancer-induced dysfunction in dendritic cells (DC), which play a central role in shaping the quantity and quality of antitumor immunity. Therefore, DC-based peptide delivery of tumor antigen is becoming a potential approach in cancer immunotherapy. In this approach, autologous DC are generated from their precursors in bone marrow or peripheral blood mononuclear cells, loaded with tumor antigen(s) and then infused back to the tumor-bearing host in about 7 days. This DC-based vaccination can act as an antigen delivery vehicle as well as a potent adjuvant, resulting in measurable antitumor immunity in several cancer settings in preclinical and clinical studies. This chapter focuses on DC-based vaccination and how this approach can be more efficacious in cancer immunotherapy.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Matzinger P (2002) The danger model: a renewed sense of self. Science 296(5566):301–305
Finn OJ (2008) Cancer immunology. N Engl J Med 358(25):2704–2715
McCarthy EF (2006) The toxins of William B. Coley and the treatment of bone and soft-tissue sarcomas. Iowa Orthop J 26:154–158
Finn OJ (2008) Immunological weapons acquired early in life win battles with cancer late in life. J Immunol 181(3):1589–1592
Pejawar-Gaddy S, Finn OJ (2008) Cancer vaccines: accomplishments and challenges. Crit Rev Oncol Hematol 67(2):93–102
Salem ML et al (2007) Tumours: immunotherapy. Encyclopedia of life sciences, 2007, John Wiley & Sons, Ltd. www.els.net
Yannelli JR, Wroblewski JM (2004) On the road to a tumor cell vaccine: 20 years of cellular immunotherapy. Vaccine 23(1):97–113
Vermorken JB et al (1999) Active specific immunotherapy for stage II and stage III human colon cancer: a randomised trial. Lancet 353(9150):345–350
Melief CJ (2008) Cancer immunotherapy by dendritic cells. Immunity 29(3):372–383
Banchereau J et al (2003) Dendritic cells: controllers of the immune system and a new promise for immunotherapy. Novartis Found Symp 252:226–235, discussion 235–228, 257–267
Stift A et al (2003) Dendritic cell-based vaccination in solid cancer. J Clin Oncol 21(1):135–142
Brossart P (2002) Dendritic cells in vaccination therapies of malignant diseases. Transfus Apher Sci 27(2):183–186
Nagorsen D, Thiel E (2006) Clinical and immunologic responses to active specific cancer vaccines in human colorectal cancer. Clin Cancer Res 12(10):3064–3069
Steinman RM, Cohn ZA (1973) Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J Exp Med 137(5):1142–1162
Rosenzwajg M et al (1996) Human dendritic cell differentiation pathway from CD34+ hematopoietic precursor cells. Blood 87(2):535–544
Strobl H et al (1996) TGF-beta 1 promotes in vitro development of dendritic cells from CD34+ hemopoietic progenitors. J Immunol 157(4):1499–1507
Yao V et al (2002) Dendritic cells. ANZ J Surg 72(7):501–506
Reid CD (1997) The dendritic cell lineage in haemopoiesis. Br J Haematol 96(2):217–223
Szabolcs P et al (1996) Dendritic cells and macrophages can mature independently from a human bone marrow-derived, post-colony-forming unit intermediate. Blood 87(11):4520–4530
Rossi G et al (1992) Development of a Langerhans cell phenotype from peripheral blood monocytes. Immunol Lett 31(2):189–197
Kasinrerk W et al (1993) CD1 molecule expression on human monocytes induced by granulocyte-macrophage colony-stimulating factor. J Immunol 150(2):579–584
Zhou LJ, Tedder TF (1996) CD14+ blood monocytes can differentiate into functionally mature CD83+ dendritic cells. Proc Natl Acad Sci USA 93(6):2588–2592
den Brok MH et al (2005) Dendritic cells: tools and targets for antitumor vaccination. Expert Rev Vaccines 4(5):699–710
Morisaki T et al (2003) Dendritic cell-based combined immunotherapy with autologous tumor-pulsed dendritic cell vaccine and activated T cells for cancer patients: rationale, current progress, and perspectives. Hum Cell 16(4):175–182
Tacken PJ et al (2007) Dendritic-cell immunotherapy: from ex vivo loading to in vivo targeting. Nat Rev Immunol 7(10):790–802
Caux C et al (1992) GM-CSF and TNF-alpha cooperate in the generation of dendritic Langerhans cells. Nature 360(6401):258–261
Cella M et al (1996) Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation. J Exp Med 184(2):747–752
Whiteside TL, Odoux C (2004) Dendritic cell biology and cancer therapy. Cancer Immunol Immunother 53(3):240–248
Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392(6673):245–252
Aarntzen EH et al (2008) Dendritic cell vaccination and immune monitoring. Cancer Immunol Immunother 57(10):1559–1568
Nicola M et al (1999) The influence of interleukin (IL)-4 and IL-13 on human dendritic cell differentiation from CD34+ progenitor cells: the importance of the source of serum. Exp Hematol 27(2):386–387
Esche C et al (1999) The use of dendritic cells for cancer vaccination. Curr Opin Mol Ther 1(1):72–81
Zhang SN et al (2011) Optimizing DC vaccination by combination with oncolytic adenovirus coexpressing IL-12 and GM-CSF. [Research Support, Non-U.S. Gov’t]. Mol Ther 19(8):1558–1568
Brinkman JA et al (2004) Peptide-based vaccines for cancer immunotherapy. Expert Opin Biol Ther 4(2):181–198
Kavanagh B et al (2007) Vaccination of metastatic colorectal cancer patients with matured dendritic cells loaded with multiple major histocompatibility complex class I peptides. J Immunother 30(7):762–772
Harley CB et al (1990) Telomeres shorten during ageing of human fibroblasts. Nature 345(6274):458–460
Cong YS et al (2002) Human telomerase and its regulation. Microbiol Mol Biol Rev 66(3):407–425
Vonderheide RH (2008) Prospects and challenges of building a cancer vaccine targeting telomerase. Biochimie 90(1):173–180
Vonderheide RH et al (2004) Vaccination of cancer patients against telomerase induces functional antitumor CD8+ T lymphocytes. Clin Cancer Res 10(3):828–839
Su Z et al (2005) Telomerase mRNA-transfected dendritic cells stimulate antigen-specific CD8+ and CD4+ T cell responses in patients with metastatic prostate cancer. J Immunol 174(6):3798–3807
Kono K et al (2002) Dendritic cells pulsed with HER-2/neu-derived peptides can induce specific T-cell responses in patients with gastric cancer. Clin Cancer Res 8(11):3394–3400
Aloysius M et al (2009) Generation in vivo of peptide-specific cytotoxic T cells and presence of regulatory T cells during vaccination with hTERT (class I and II) peptide-pulsed DCs. [Research Support, Non-U.S. Gov’t]. J Transl Med 7:18
Suso EM et al (2011) hTERT mRNA dendritic cell vaccination: complete response in a pancreatic cancer patient associated with response against several hTERT epitopes. Cancer Immunol Immunother 60(6):809–818
Terada T et al (1996) Expression of MUC apomucins in normal pancreas and pancreatic tumours. J Pathol 180(2):160–165
Taylor-Papadimitriou J et al (1999) MUC1 and cancer. Biochim Biophys Acta 1455(2–3):301–313
Brossart P et al (2001) The epithelial tumor antigen MUC1 is expressed in hematological malignancies and is recognized by MUC1-specific cytotoxic T-lymphocytes. Cancer Res 61(18):6846–6850
Jerome KR et al (1993) Tumor-specific cytotoxic T cell clones from patients with breast and pancreatic adenocarcinoma recognize EBV-immortalized B cells transfected with polymorphic epithelial mucin complementary DNA. J Immunol 151(3):1654–1662
Yamamoto K et al (2005) MUC1 peptide vaccination in patients with advanced pancreas or biliary tract cancer. Anticancer Res 25(5):3575–3579
Brossart P et al (2000) Induction of cytotoxic T-lymphocyte responses in vivo after vaccinations with peptide-pulsed dendritic cells. Blood 96(9):3102–3108
Brossart P, Bevan MJ (1997) Presentation of exogenous protein antigens on major histocompatibility complex class I molecules by dendritic cells: pathway of presentation and regulation by cytokines. Blood 90(4):1594–1599
Wierecky J et al (2006) Immunologic and clinical responses after vaccinations with peptide-pulsed dendritic cells in metastatic renal cancer patients. Cancer Res 66(11):5910–5918
Kim Y et al (2003) Gastrointestinal tract cancer screening using fecal carcinoembryonic antigen. Ann Clin Lab Sci 33(1):32–38
Kaufman HL et al (2007) Poxvirus-based vaccine therapy for patients with advanced pancreatic cancer. J Transl Med 5:60
Tassi E et al (2008) Carcinoembryonic antigen-specific but not antiviral CD4+ T cell immunity is impaired in pancreatic carcinoma patients. J Immunol 181(9):6595–6603
Ueda Y et al (2004) Dendritic cell-based immunotherapy of cancer with carcinoembryonic antigen-derived, HLA-A24-restricted CTL epitope: clinical outcomes of 18 patients with metastatic gastrointestinal or lung adenocarcinomas. [Clinical trial]. Int J Oncol 24(4):909–917
Liu KJ et al (2004) Generation of carcinoembryonic antigen (CEA)-specific T-cell responses in HLA-A*0201 and HLA-A*2402 late-stage colorectal cancer patients after vaccination with dendritic cells loaded with CEA peptides. Clin Cancer Res 10(8):2645–2651
Babatz J et al (2006) Induction of cellular immune responses against carcinoembryonic antigen in patients with metastatic tumors after vaccination with altered peptide ligand-loaded dendritic cells. Cancer Immunol Immunother 55(3):268–276
Lesterhuis WJ et al (2006) Vaccination of colorectal cancer patients with CEA-loaded dendritic cells: antigen-specific T cell responses in DTH skin tests. Ann Oncol 17(6):974–980
Lesterhuis WJ et al (2008) Dendritic cell vaccines in melanoma: from promise to proof? Crit Rev Oncol Hematol 66(2):118–134
Lesterhuis WJ et al (2010) Immunogenicity of dendritic cells pulsed with CEA peptide or transfected with CEA mRNA for vaccination of colorectal cancer patients. Anticancer Res 30(12):5091–5097
Ambrosini G et al (1997) A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 3(8):917–921
Lopes RB et al (2007) Expression of the IAP protein family is dysregulated in pancreatic cancer cells and is important for resistance to chemotherapy. Int J Cancer 120(11):2344–2352
Casati C et al (2003) The apoptosis inhibitor protein survivin induces tumor-specific CD8+ and CD4+ T cells in colorectal cancer patients. Cancer Res 63(15):4507–4515
Otto K et al (2005) Lack of toxicity of therapy-induced T cell responses against the universal tumour antigen survivin. Vaccine 23(7):884–889
Tsuruma T et al (2004) Phase I clinical study of anti-apoptosis protein, survivin-derived peptide vaccine therapy for patients with advanced or recurrent colorectal cancer. J Transl Med 2(1):19
Tsuruma T et al (2008) Clinical and immunological evaluation of anti-apoptosis protein, survivin-derived peptide vaccine in phase I clinical study for patients with advanced or recurrent breast cancer. J Transl Med 6:24
Karanikas V et al (2008) Baseline levels of CD8+ T cells against survivin and survivin-2B in the blood of lung cancer patients and cancer-free individuals. Clin Immunol 129(2):230–240
Wobser M et al (2006) Complete remission of liver metastasis of pancreatic cancer under vaccination with a HLA-A2 restricted peptide derived from the universal tumor antigen survivin. Cancer Immunol Immunother 55(10):1294–1298
Nagaraj S et al (2007) Dendritic cell-based full-length survivin vaccine in treatment of experimental tumors. J Immunother 30(2):169–179
Eggert AA et al (1999) Biodistribution and vaccine efficiency of murine dendritic cells are dependent on the route of administration. Cancer Res 59(14):3340–3345
Moyer JS et al (2008) Intratumoral dendritic cells and chemoradiation for the treatment of murine squamous cell carcinoma. J Immunother 31(9):885–895
Rossowska J et al (2007) Tissue localization of tumor antigen-loaded mouse dendritic cells applied as an anti-tumor vaccine and their influence on immune response. Folia Histochem Cytobiol 45(4):349–355
Cohen S et al (2009) Dendritic cell-based therapeutic vaccination against myeloma: vaccine formulation determines efficacy against light chain myeloma. J Immunol 182(3):1667–1673
De Vries IJ et al (2003) Effective migration of antigen-pulsed dendritic cells to lymph nodes in melanoma patients is determined by their maturation state. Cancer Res 63(1):12–17
Trakatelli M et al (2006) A new dendritic cell vaccine generated with interleukin-3 and interferon-beta induces CD8+ T cell responses against NA17-A2 tumor peptide in melanoma patients. Cancer Immunol Immunother 55(4):469–474
Zitvogel L, Tursz T (2005) In vivo veritas. Nat Biotechnol 23(11):1372–1374
Bedrosian I et al (2003) Intranodal administration of peptide-pulsed mature dendritic cell vaccines results in superior CD8+ T-cell function in melanoma patients. J Clin Oncol 21(20):3826–3835
Kyte JA et al (2006) Phase I/II trial of melanoma therapy with dendritic cells transfected with autologous tumor-mRNA. Cancer Gene Ther 13(10):905–918
Fong L et al (2001) Dendritic cells injected via different routes induce immunity in cancer patients. J Immunol 166(6):4254–4259
Mullins DW et al (2003) Route of immunization with peptide-pulsed dendritic cells controls the distribution of memory and effector T cells in lymphoid tissues and determines the pattern of regional tumor control. J Exp Med 198(7):1023–1034
Adema GJ et al (2005) Migration of dendritic cell based cancer vaccines: in vivo veritas? Curr Opin Immunol 17(2):170–174
Liau LM et al (2005) Dendritic cell vaccination in glioblastoma patients induces systemic and intracranial T-cell responses modulated by the local central nervous system tumor microenvironment. Clin Cancer Res 11(15):5515–5525
Palmer DH et al (2009) A phase II study of adoptive immunotherapy using dendritic cells pulsed with tumor lysate in patients with hepatocellular carcinoma. Hepatology 49(1):124–132
Trepiakas R et al (2010) Vaccination with autologous dendritic cells pulsed with multiple tumor antigens for treatment of patients with malignant melanoma: results from a phase I/II trial. Cytotherapy 12(6):721–734
Waisman A, Yogev N (2009) B7-H1 and CD8+ Treg: the enigmatic role of B7-H1 in peripheral tolerance. Eur J Immunol 39(6):1448–1451
Yoshimura A (2009) Regulation of cytokine signaling by the SOCS and Spred family proteins. Keio J Med 58(2):73–83
Lob S, Konigsrainer A (2008) Is IDO a key enzyme bridging the gap between tumor escape and tolerance induction? Langenbecks Arch Surg 393(6):995–1003
Mahnke K et al (2007) Tolerogenic dendritic cells and regulatory T cells: a two-way relationship. J Dermatol Sci 46(3):159–167
Marigo I et al (2008) Tumor-induced tolerance and immune suppression by myeloid derived suppressor cells. Immunol Rev 222:162–179
Li H et al (2009) Cancer-expanded myeloid-derived suppressor cells induce anergy of NK cells through membrane-bound TGF-beta 1. J Immunol 182(1):240–249
Bronte V, Mocellin S (2009) Suppressive influences in the immune response to cancer. J Immunother 32(1):1–11
Llopiz D et al (2009) Peptide inhibitors of transforming growth factor-beta enhance the efficacy of antitumor immunotherapy. Int J Cancer 125(11):2614–2623
Pellegrini M et al (2009) Adjuvant IL-7 antagonizes multiple cellular and molecular inhibitory networks to enhance immunotherapies. Nat Med 15(5):528–536
Vogt TK et al (2009) Novel function for interleukin-7 in dendritic cell development. Blood 113(17):3961–3968
Gabrilovich DI, Nagaraj S (2009) Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 9(3):162–174
Lechner MG et al (2011) Functional characterization of human Cd33+ and Cd11b+ myeloid-derived suppressor cell subsets induced from peripheral blood mononuclear cells co-cultured with a diverse set of human tumor cell lines. J Transl Med 9:90
Chatila TA (2009) Regulatory T cells: key players in tolerance and autoimmunity. Endocrinol Metab Clin North Am 38(2):265–272
Mills KH (2004) Regulatory T cells: friend or foe in immunity to infection? Nat Rev Immunol 4(11):841–855
Sakaguchi S (2005) Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat Immunol 6(4):345–352
Zhou G et al (2006) Amplification of tumor-specific regulatory T cells following therapeutic cancer vaccines. Blood 107(2):628–636
Xu L et al (2011) In situ prior proliferation of CD4+ CCR6+ regulatory T cells facilitated by TGF-beta secreting DC is crucial for their enrichment and suppression in tumor immunity. PLoS One 6(5):1–10
Diaz-Montero CM et al (2009) Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother 58(1):49–59
Stewart TJ, Smyth MJ (2011) Improving cancer immunotherapy by targeting tumor-induced immune suppression. Cancer Metastasis Rev 30(1):125–140
Bak SP et al (2008) Murine ovarian cancer vascular leukocytes require arginase-1 activity for T cell suppression. Mol Immunol 46(2):258–268
Corzo CA et al (2009) Mechanism regulating reactive oxygen species in tumor-induced myeloid-derived suppressor cells. J Immunol 182(9):5693–5701
Ray P et al (2011) Lung myeloid-derived suppressor cells and regulation of inflammation. Immunol Res 50(2–3):153–158
Wang Z et al (2008) Short-term anti-CD25 monoclonal antibody treatment and neogenetic CD4(+)CD25(high) regulatory T cells in kidney transplantation. Transpl Immunol 19(1):69–73
Yang L et al (2004) Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis. Cancer Cell 6(4):409–421
Finke J et al (2011) MDSC as a mechanism of tumor escape from sunitinib mediated anti-angiogenic therapy. Int Immunopharmacol 11(7):856–861
Ko JS et al (2009) Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients. Clin Cancer Res 15(6):2148–2157
Kusmartsev S et al (2008) Reversal of myeloid cell-mediated immunosuppression in patients with metastatic renal cell carcinoma. Clin Cancer Res 14(24):8270–8278
Qian F et al (2009) Efficacy of levo-1-methyl tryptophan and dextro-1-methyl tryptophan in reversing indoleamine-2,3-dioxygenase-mediated arrest of T-cell proliferation in human epithelial ovarian cancer. Cancer Res 69(13):5498–5504
Wang RF et al (2008) Toll-like receptors and immune regulation: implications for cancer therapy. Oncogene 27(2):181–189
Platz KP et al (2005) IL-2 antagonists: the European perspective. Transplant Proc 37(4):1783–1784
Duvic M, Talpur R (2008) Optimizing denileukin diftitox (Ontak) therapy. Future Oncol 4(4):457–469
Ozao-Choy J et al (2009) The novel role of tyrosine kinase inhibitor in the reversal of immune suppression and modulation of tumor microenvironment for immune-based cancer therapies. Cancer Res 69(6):2514–2522
Chen YL et al (2008) Depletion of CD4(+)CD25(+) regulatory T cells can promote local immunity to suppress tumor growth in benzo[a]pyrene-induced forestomach carcinoma. World J Gastroenterol 14(38):5797–5809
Vonderheide RH, June CH (2003) A translational bridge to cancer immunotherapy: exploiting costimulation and target antigens for active and passive T cell immunotherapy. Immunol Res 27(2–3):341–356
Kowalczyk DW (2002) Tumors and the danger model. Acta Biochim Pol 49(2):295–302
Kawai T, Akira S (2007) TLR signaling. Semin Immunol 19(1):24–32
Seya T et al (2006) Role of Toll-like receptors in adjuvant-augmented immune therapies. Evid Based Complement Alternat Med 3(1):31–38, discussion 133–137
Salem ML et al (2009) Recovery from cyclophosphamide-induced lymphopenia results in expansion of immature dendritic cells which can mediate enhanced prime-boost vaccination antitumor responses in vivo when stimulated with the TLR3 agonist poly(I:C). J Immunol 182(4):2030–2040
Salem ML et al (2009) The TLR3 agonist poly(I:C) targets CD8+ T cells and augments their antigen-specific responses upon their adoptive transfer into naive recipient mice. Vaccine 27(4):549–557
Salem ML et al (2006) The adjuvant effects of the toll-like receptor 3 ligand polyinosinic-cytidylic acid poly(I:C) on antigen-specific CD8+ T cell responses are partially dependent on NK cells with the induction of a beneficial cytokine milieu. Vaccine 24(24):5119–5132
Salem ML et al (2005) Defining the antigen-specific T-cell response to vaccination and poly(I:C)/TLR3 signaling: evidence of enhanced primary and memory CD8 T-cell responses and antitumor immunity. J Immunother 28(3):220–228
Salem ML et al (2007) Defining the ability of cyclophosphamide preconditioning to enhance the antigen-specific CD8+ T-cell response to peptide vaccination: creation of a beneficial host microenvironment involving type I IFNs and myeloid cells. J Immunother 30(1):40–53
Banchereau J, Palucka AK (2005) Dendritic cells as therapeutic vaccines against cancer. Nat Rev Immunol 5(4):296–306
Fajardo-Moser M et al (2008) Mechanisms of dendritic cell-based vaccination against infection. Int J Med Microbiol 298(1–2):11–20
Datta SK et al (2003) A subset of Toll-like receptor ligands induces cross-presentation by bone marrow-derived dendritic cells. J Immunol 170(8):4102–4110
Edwards AD et al (2003) Toll-like receptor expression in murine DC subsets: lack of TLR7 expression by CD8 alpha+ DC correlates with unresponsiveness to imidazoquinolines. Eur J Immunol 33(4):827–833
Lore K et al (2003) Toll-like receptor ligands modulate dendritic cells to augment cytomegalovirus- and HIV-1-specific T cell responses. J Immunol 171(8):4320–4328
Kadowaki N et al (2001) Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens. J Exp Med 194(6):863–869
West MA et al (2004) Enhanced dendritic cell antigen capture via toll-like receptor-induced actin remodeling. Science 305(5687):1153–1157
Meyer T, Stockfleth E (2008) Clinical investigations of Toll-like receptor agonists. Expert Opin Investig Drugs 17(7):1051–1065
Boullart AC et al (2008) Maturation of monocyte-derived dendritic cells with Toll-like receptor 3 and 7/8 ligands combined with prostaglandin E2 results in high interleukin-12 production and cell migration. Cancer Immunol Immunother 57(11):1589–1597
Jasani B et al (2009) Ampligen: a potential toll-like 3 receptor adjuvant for immunotherapy of cancer. Vaccine 27(25–26):3401–3404
Renn CN et al (2006) TLR activation of Langerhans cell-like dendritic cells triggers an antiviral immune response. J Immunol 177(1):298–305
Tirapu I et al (2009) PolyI:C-induced reduction in uptake of soluble antigen is independent of dendritic cell activation. Int Immunol 21(7):871–879
Walker J, Tough DF (2006) Modification of TLR-induced activation of human dendritic cells by type I IFN: synergistic interaction with TLR4 but not TLR3 agonists. Eur J Immunol 36(7):1827–1836
Adams M et al (2003) Dendritic cell (DC) based therapy for cervical cancer: use of DC pulsed with tumour lysate and matured with a novel synthetic clinically non-toxic double stranded RNA analogue poly [I]:poly [C(12)U] (Ampligen R). Vaccine 21(7–8):787–790
Mailliard RB et al (2004) Alpha-type-1 polarized dendritic cells: a novel immunization tool with optimized CTL-inducing activity. Cancer Res 64(17):5934–5937
Navabi H et al (2009) A clinical grade poly I:C-analogue (Ampligen) promotes optimal DC maturation and Th1-type T cell responses of healthy donors and cancer patients in vitro. Vaccine 27(1):107–115
Zhu X et al (2007) Toll like receptor-3 ligand poly-ICLC promotes the efficacy of peripheral vaccinations with tumor antigen-derived peptide epitopes in murine CNS tumor models. J Transl Med 5:10
Austyn JM (1998) Dendritic cells. Curr Opin Hematol 5(1):3–15
Satthaporn S, Eremin O (2001) Dendritic cells (I): biological functions. J R Coll Surg Edinb 46(1):9–19
Satthaporn S, Eremin O (2001) Dendritic cells (II): role and therapeutic implications in cancer. J R Coll Surg Edinb 46(3):159–167
Shortman K, Caux C (1997) Dendritic cell development: multiple pathways to nature’s adjuvants. Stem Cells 15(6):409–419
Shortman K et al (1997) Dendritic cells and T lymphocytes: developmental and functional interactions. Ciba Found Symp 204:130–138, discussion 138–141
Schmidt J et al (2007) Intratumoural injection of the toll-like receptor-2/6 agonist ‘macrophage-activating lipopeptide-2’ in patients with pancreatic carcinoma: a phase I/II trial. Br J Cancer 97(5):598–604
Schneider C et al (2004) Tumour suppression induced by the macrophage activating lipopeptide MALP-2 in an ultrasound guided pancreatic carcinoma mouse model. Gut 53(3):355–361
Schill T et al (2012) Stimulation of pulmonary immune responses by the TLR2/6 agonist MALP-2 and effect on melanoma metastasis to the lung. Exp Dermatol 21(2):91–98
Pratesi G et al (2005) Therapeutic synergism of gemcitabine and CpG-oligodeoxynucleotides in an orthotopic human pancreatic carcinoma xenograft. Cancer Res 65(14):6388–6393
Vanderlocht J et al (2010) Increased tumor-specific CD8+ T cell induction by dendritic cells matured with a clinical grade TLR-agonist in combination with IFN-gamma. Int J Immunopathol Pharmacol 23(1):35–50
Okamoto M, Sato M (2003) Toll-like receptor signaling in anti-cancer immunity. J Med Invest 50(1–2):9–24
Osada T et al (2006) Dendritic cell-based immunotherapy. Int Rev Immunol 25(5–6):377–413
Cheever MA (2008) Twelve immunotherapy drugs that could cure cancers. Immunol Rev 222:357–368
Cheever MA et al (2008) Translational Research Working Group developmental pathway for immune response modifiers. Clin Cancer Res 14(18):5692–5699
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer Science+Business Media New York
About this protocol
Cite this protocol
Salem, M.L. (2014). The Use of Dendritic Cells for Peptide-Based Vaccination in Cancer Immunotherapy. In: Lawman, M., Lawman, P. (eds) Cancer Vaccines. Methods in Molecular Biology, vol 1139. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-0345-0_37
Download citation
DOI: https://doi.org/10.1007/978-1-4939-0345-0_37
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-0344-3
Online ISBN: 978-1-4939-0345-0
eBook Packages: Springer Protocols