Advertisement

Cell Therapy pp 99-120 | Cite as

Dendritic Cell-Based Cancer Therapies: Current Status and Future Directions

  • Shah Md. Shahjahan Miah
  • Timothy K. Erick
  • Dwaine F. EmerichEmail author
Chapter
Part of the Molecular and Translational Medicine book series (MOLEMED)

Abstract

Cancer immunotherapy is a growing field that focuses on manipulating the immune system to better target cancer. Dendritic cells (DCs) have been identified as a potential component of cancer vaccines. DCs present tumor-specific antigens to T cells in order to generate tumor-specific immunity. Animal model experiments have shown that DCs loaded with tumor antigen ex vivo and administered into tumor-bearing hosts can elicit tumor-specific T cell-mediated clearance of tumor targets. In human cancer patients, antigen-loaded DCs have been tested in multiple clinical trials as therapeutic vaccines. Clinical trials in patients with several different cancers, including malignant lymphoma, melanoma, and prostate cancer, have suggested that DC-mediated antigen presentation leads to increased anticancer immunity. For these trials, there are some important considerations: selection of the tumor-specific antigen, efficient introduction of the antigen into DCs for processing and presentation to the activated T cells, preparation of the correct amount of DCs, and route of administration of DCs to patients. With further research and refinement, DC vaccination may prove both efficacious and widely applicable to human tumors.

Keywords

Dendritic cells (DCs) Immunotherapy Cancer Tumor Immune system Vaccine Antigen presentation 

Abbreviations

APC

Antigen-presenting cell

cDC

Conventional DC

CTL

Cytotoxic T lymphocyte

CTLA-4

Cytotoxic T lymphocyte antigen 4

DC

Dendritic cell

iDC

Immature DC

IFN

Interferon

IL

Interleukin

KLH

Keyhole limpet hemocyanin

mDC

Mature DC

PD-1

Programmed death receptor-1

pDC

Plasmacytoid DC

TLR

Toll-like receptor

References

  1. 1.
    Riedel S. Edward Jenner and the history of smallpox and vaccination. Proc (Bayl Univ Med Cent). 2005;18(1):21–5.Google Scholar
  2. 2.
    Nabel GJ. Designing tomorrow’s vaccines. N Engl J Med. 2013;368(6):551–60.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Pulendran B, Ahmed R. Immunological mechanisms of vaccination. Nat Immunol. 2011;12(6):509–17.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Guo C, Manjili MH, Subjeck JR, Sarkar D, Fisher PB, Wang XY. Therapeutic cancer vaccines: past, present, and future. Adv Cancer Res. 2013;119:421–75.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Sudhakar A. History of cancer, ancient and modern treatment methods. J Cancer Sci Ther. 2009;1(2):1–4.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Appay V, Douek DC, Price DA. CD8+ T cell efficacy in vaccination and disease. Nat Med. 2008;14(6):623–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Mullins IM, Slingluff CL, Lee JK, Garbee CF, Shu J, Anderson SG, et al. CXC chemokine receptor 3 expression by activated CD8+ T cells is associated with survival in melanoma patients with stage III disease. Cancer Res. 2004;64(21):7697–701.PubMedCrossRefGoogle Scholar
  8. 8.
    Le Floc’h A, Jalil A, Vergnon I, Le Maux Chansac B, Lazar V, Bismuth G, et al. Alpha E beta 7 integrin interaction with E-cadherin promotes antitumor CTL activity by triggering lytic granule polarization and exocytosis. J Exp Med. 2007;204(3):559–70.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Sandoval F, Terme M, Nizard M, Badoual C, Bureau MF, Freyburger L, et al. Mucosal imprinting of vaccine-induced CD8(+) T cells is crucial to inhibit the growth of mucosal tumors. Sci Transl Med. 2013;5(172):172ra20.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Wilcox RA, Flies DB, Zhu G, Johnson AJ, Tamada K, Chapoval AI, et al. Provision of antigen and CD137 signaling breaks immunological ignorance, promoting regression of poorly immunogenic tumors. J Clin Invest. 2002;109(5):651–9.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Peggs KS, Quezada SA, Chambers CA, Korman AJ, Allison JP. Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies. J Exp Med. 2009;206(8):1717–25.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Freeman GJ, Wherry EJ, Ahmed R, Sharpe AH. Reinvigorating exhausted HIV-specific T cells via PD-1-PD-1 ligand blockade. J Exp Med. 2006;203(10):2223–7.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Joffre OP, Segura E, Savina A, Amigorena S. Cross-presentation by dendritic cells. Nat Rev Immunol. 2012;12(8):557–69.PubMedCrossRefGoogle Scholar
  14. 14.
    Lizee G, Overwijk WW, Radvanyi L, Gao J, Sharma P, Hwu P. Harnessing the power of the immune system to target cancer. Annu Rev Med. 2013;64:71–90.PubMedCrossRefGoogle Scholar
  15. 15.
    Spolski R, Kashyap M, Robinson C, Yu Z, Leonard WJ. IL-21 signaling is critical for the development of type I diabetes in the NOD mouse. Proc Natl Acad Sci U S A. 2008;105(37):14028–33.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Palucka K, Banchereau J. Dendritic-cell-based therapeutic cancer vaccines. Immunity. 2013;39(1):38–48.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    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(5):1142–62.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Steinman RM, Nussenzweig MC. Dendritic cells: features and functions. Immunol Rev. 1980;53:127–47.PubMedCrossRefGoogle Scholar
  19. 19.
    Butterfield LH. Dendritic cells in cancer immunotherapy clinical trials: are we making progress? Front Immunol. 2013;4:454.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature. 1998;392(6673):245–52.PubMedCrossRefGoogle Scholar
  21. 21.
    Steinman RM, Hawiger D, Nussenzweig MC. Tolerogenic dendritic cells. Annu Rev Immunol. 2003;21:685–711.PubMedCrossRefGoogle Scholar
  22. 22.
    Merad M, Sathe P, Helft J, Miller J, Mortha A. The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu Rev Immunol. 2013;31:563–604.PubMedCrossRefGoogle Scholar
  23. 23.
    Swiecki M, Colonna M. The multifaceted biology of plasmacytoid dendritic cells. Nat Rev Immunol. 2015;15(8):471–85.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Goubier A, Dubois B, Gheit H, Joubert G, Villard-Truc F, Asselin-Paturel C, et al. Plasmacytoid dendritic cells mediate oral tolerance. Immunity. 2008;29(3):464–75.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Guilliams M, Henri S, Tamoutounour S, Ardouin L, Schwartz-Cornil I, Dalod M, et al. From skin dendritic cells to a simplified classification of human and mouse dendritic cell subsets. Eur J Immunol. 2010;40(8):2089–94.PubMedCrossRefGoogle Scholar
  26. 26.
    Merad M, Ginhoux F, Collin M. Origin, homeostasis and function of Langerhans cells and other langerin-expressing dendritic cells. Nat Rev Immunol. 2008;8(12):935–47.PubMedCrossRefGoogle Scholar
  27. 27.
    Igyarto BZ, Haley K, Ortner D, Bobr A, Gerami-Nejad M, Edelson BT, et al. Skin-resident murine dendritic cell subsets promote distinct and opposing antigen-specific T helper cell responses. Immunity. 2011;35(2):260–72.PubMedCrossRefGoogle Scholar
  28. 28.
    van der Vlist M, de Witte L, de Vries RD, Litjens M, de Jong MA, Fluitsma D, et al. Human Langerhans cells capture measles virus through Langerin and present viral antigens to CD4(+) T cells but are incapable of cross-presentation. Eur J Immunol. 2011;41(9):2619–31.PubMedCrossRefGoogle Scholar
  29. 29.
    Stoitzner P, Tripp CH, Eberhart A, Price KM, Jung JY, Bursch L, et al. Langerhans cells cross-present antigen derived from skin. Proc Natl Acad Sci U S A. 2006;103(20):7783–8.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Bursch LS, Rich BE, Hogquist KA. Langerhans cells are not required for the CD8 T cell response to epidermal self-antigens. J Immunol. 2009;182(8):4657–64.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Segura E, Amigorena S. Inflammatory dendritic cells in mice and humans. Trends Immunol. 2013;34(9):440–5.PubMedCrossRefGoogle Scholar
  32. 32.
    Segura E, Touzot M, Bohineust A, Cappuccio A, Chiocchia G, Hosmalin A, et al. Human inflammatory dendritic cells induce Th17 cell differentiation. Immunity. 2013;38(2):336–48.PubMedCrossRefGoogle Scholar
  33. 33.
    Nakano H, Lin KL, Yanagita M, Charbonneau C, Cook DN, Kakiuchi T, et al. Blood-derived inflammatory dendritic cells in lymph nodes stimulate acute T helper type 1 immune responses. Nat Immunol. 2009;10(4):394–402.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Copin R, De Baetselier P, Carlier Y, Letesson JJ, Muraille E. MyD88-dependent activation of B220-CD11b+LY-6C+ dendritic cells during Brucella melitensis infection. J Immunol. 2007;178(8):5182–91.PubMedCrossRefGoogle Scholar
  35. 35.
    Kool M, Soullie T, van Nimwegen M, Willart MA, Muskens F, Jung S, et al. Alum adjuvant boosts adaptive immunity by inducing uric acid and activating inflammatory dendritic cells. J Exp Med. 2008;205(4):869–82.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Mineharu Y, King GD, Muhammad AK, Bannykh S, Kroeger KM, Liu C, et al. Engineering the brain tumor microenvironment enhances the efficacy of dendritic cell vaccination: implications for clinical trial design. Clin Cancer Res. 2011;17(14):4705–18.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Driessens G, Kline J, Gajewski TF. Costimulatory and coinhibitory receptors in anti-tumor immunity. Immunol Rev. 2009;229(1):126–44.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Strauss L, Bergmann C, Szczepanski MJ, Lang S, Kirkwood JM, Whiteside TL. Expression of ICOS on human melanoma-infiltrating CD4+CD25highFoxp3+ T regulatory cells: implications and impact on tumor-mediated immune suppression. J Immunol. 2008;180(5):2967–80.PubMedCrossRefGoogle Scholar
  39. 39.
    Greenwald RJ, Freeman GJ, Sharpe AH. The B7 family revisited. Annu Rev Immunol. 2005;23:515–48.PubMedCrossRefGoogle Scholar
  40. 40.
    Sica GL, Choi IH, Zhu G, Tamada K, Wang SD, Tamura H, et al. B7-H4, a molecule of the B7 family, negatively regulates T cell immunity. Immunity. 2003;18(6):849–61.PubMedCrossRefGoogle Scholar
  41. 41.
    Grewal IS, Flavell RA. CD40 and CD154 in cell-mediated immunity. Annu Rev Immunol. 1998;16:111–35.PubMedCrossRefGoogle Scholar
  42. 42.
    Watts TH. TNF/TNFR family members in costimulation of T cell responses. Annu Rev Immunol. 2005;23:23–68.PubMedCrossRefGoogle Scholar
  43. 43.
    Croft M. Costimulation of T cells by OX40, 4-1BB, and CD27. Cytokine Growth Factor Rev. 2003;14(3–4):265–73.PubMedCrossRefGoogle Scholar
  44. 44.
    Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Grauer OM, Molling JW, Bennink E, Toonen LW, Sutmuller RP, Nierkens S, et al. TLR ligands in the local treatment of established intracerebral murine gliomas. J Immunol. 2008;181(10):6720–9.PubMedCrossRefGoogle Scholar
  46. 46.
    Dearman RJ, Cumberbatch M, Maxwell G, Basketter DA, Kimber I. Toll-like receptor ligand activation of murine bone marrow-derived dendritic cells. Immunology. 2009;126(4):475–84.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Zhao BG, Vasilakos JP, Tross D, Smirnov D, Klinman DM. Combination therapy targeting toll like receptors 7, 8 and 9 eliminates large established tumors. J Immunother Cancer. 2014;2:12.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Hunn MK, Hermans IF. Exploiting invariant NKT cells to promote T-cell responses to cancer vaccines. Oncoimmunology. 2013;2(4):e23789.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Latchman Y, Wood CR, Chernova T, Chaudhary D, Borde M, Chernova I, et al. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol. 2001;2(3):261–8.PubMedCrossRefGoogle Scholar
  50. 50.
    Boudreau JE, Bonehill A, Thielemans K, Wan Y. Engineering dendritic cells to enhance cancer immunotherapy. Mol Ther. 2011;19(5):841–53.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    JH G, Li G. Dendritic cell-based immunotherapy for malignant glioma. Neurosci Bull. 2008;24(1):39–44.CrossRefGoogle Scholar
  52. 52.
    Neller MA, Lopez JA, Schmidt CW. Antigens for cancer immunotherapy. Semin Immunol. 2008;20(5):286–95.PubMedCrossRefGoogle Scholar
  53. 53.
    Eyrich M, Rachor J, Schreiber SC, Wolfl M, Schlegel PG. Dendritic cell vaccination in pediatric gliomas: lessons learnt and future perspectives. Front Pediatr. 2013;1:12.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Akasaki Y, Liu G, Chung NH, Ehtesham M, Black KL, Yu JS. Induction of a CD4+ T regulatory type 1 response by cyclooxygenase-2-overexpressing glioma. J Immunol. 2004;173(7):4352–9.PubMedCrossRefGoogle Scholar
  55. 55.
    Palucka K, Banchereau J. Cancer immunotherapy via dendritic cells. Nat Rev Cancer. 2012;12(4):265–77.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Diamond MS, Kinder M, Matsushita H, Mashayekhi M, Dunn GP, Archambault JM, et al. Type I interferon is selectively required by dendritic cells for immune rejection of tumors. J Exp Med. 2011;208(10):1989–2003.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Fuertes MB, Kacha AK, Kline J, Woo SR, Kranz DM, Murphy KM, et al. Host type I IFN signals are required for antitumor CD8+ T cell responses through CD8{alpha}+ dendritic cells. J Exp Med. 2011;208(10):2005–16.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Martin-Fontecha A, Thomsen LL, Brett S, Gerard C, Lipp M, Lanzavecchia A, et al. Induced recruitment of NK cells to lymph nodes provides IFN-gamma for T(H)1 priming. Nat Immunol. 2004;5(12):1260–5.PubMedCrossRefGoogle Scholar
  59. 59.
    Lion E, Smits EL, Berneman ZN, Van Tendeloo VF. NK cells: key to success of DC-based cancer vaccines? Oncologist. 2012;17(10):1256–70.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Boudreau JE, Bridle BW, Stephenson KB, Jenkins KM, Brunelliere J, Bramson JL, et al. Recombinant vesicular stomatitis virus transduction of dendritic cells enhances their ability to prime innate and adaptive antitumor immunity. Mol Ther. 2009;17(8):1465–72.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Dhodapkar MV, Dhodapkar KM, Palucka AK. Interactions of tumor cells with dendritic cells: balancing immunity and tolerance. Cell Death Differ. 2008;15(1):39–50.PubMedCrossRefGoogle Scholar
  62. 62.
    Tran Janco JM, Lamichhane P, Karyampudi L, Knutson KL. Tumor-infiltrating dendritic cells in cancer pathogenesis. J Immunol. 2015;194(7):2985–91.PubMedCrossRefGoogle Scholar
  63. 63.
    Chao MP, Alizadeh AA, Tang C, Myklebust JH, Varghese B, Gill S, et al. Anti-CD47 antibody synergizes with rituximab to promote phagocytosis and eradicate non-Hodgkin lymphoma. Cell. 2010;142(5):699–713.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Chomarat P, Banchereau J, Davoust J, Palucka AK. IL-6 switches the differentiation of monocytes from dendritic cells to macrophages. Nat Immunol. 2000;1(6):510–4.PubMedCrossRefGoogle Scholar
  65. 65.
    Hiltbold EM, Vlad AM, Ciborowski P, Watkins SC, Finn OJ. The mechanism of unresponsiveness to circulating tumor antigen MUC1 is a block in intracellular sorting and processing by dendritic cells. J Immunol. 2000;165(7):3730–41.PubMedCrossRefGoogle Scholar
  66. 66.
    Kawamura K, Bahar R, Natsume W, Sakiyama S, Tagawa M. Secretion of interleukin-10 from murine colon carcinoma cells suppresses systemic antitumor immunity and impairs protective immunity induced against the tumors. Cancer Gene Ther. 2002;9(1):109–15.PubMedCrossRefGoogle Scholar
  67. 67.
    Corinti S, Albanesi C, la Sala A, Pastore S, Girolomoni G. Regulatory activity of autocrine IL-10 on dendritic cell functions. J Immunol. 2001;166(7):4312–8.PubMedCrossRefGoogle Scholar
  68. 68.
    Ogata M, Ito T, Shimamoto K, Nakanishi T, Satsutani N, Miyamoto R, et al. Plasmacytoid dendritic cells have a cytokine-producing capacity to enhance ICOS ligand-mediated IL-10 production during T-cell priming. Int Immunol. 2013;25(3):171–82.PubMedCrossRefGoogle Scholar
  69. 69.
    Cao W, Bover L, Cho M, Wen X, Hanabuchi S, Bao M, et al. Regulation of TLR7/9 responses in plasmacytoid dendritic cells by BST2 and ILT7 receptor interaction. J Exp Med. 2009;206(7):1603–14.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Anguille S, Smits EL, Lion E, van Tendeloo VF, Berneman ZN. Clinical use of dendritic cells for cancer therapy. Lancet Oncol. 2014;15(7):e257–67.PubMedCrossRefGoogle Scholar
  71. 71.
    Sallusto F, Lanzavecchia A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J Exp Med. 1994;179(4):1109–18.PubMedCrossRefGoogle Scholar
  72. 72.
    Jonuleit H, Kuhn U, Muller G, Steinbrink K, Paragnik L, Schmitt E, et al. Pro-inflammatory cytokines and prostaglandins induce maturation of potent immunostimulatory dendritic cells under fetal calf serum-free conditions. Eur J Immunol. 1997;27(12):3135–42.PubMedCrossRefGoogle Scholar
  73. 73.
    de Vries IJ, Eggert AA, Scharenborg NM, Vissers JL, Lesterhuis WJ, Boerman OC, et al. Phenotypical and functional characterization of clinical grade dendritic cells. J Immunother. 2002;25(5):429–38.PubMedCrossRefGoogle Scholar
  74. 74.
    Romani N, Gruner S, Brang D, Kampgen E, Lenz A, Trockenbacher B, et al. Proliferating dendritic cell progenitors in human blood. J Exp Med. 1994;180(1):83–93.PubMedCrossRefGoogle Scholar
  75. 75.
    Tawab A, Fan Y, Read EJ, Kurlander RJ. Effect of ex vivo culture duration on phenotype and cytokine production by mature dendritic cells derived from peripheral blood monocytes. Transfusion. 2009;49(3):536–47.PubMedCrossRefGoogle Scholar
  76. 76.
    Timmerman JM, Levy R. Linkage of foreign carrier protein to a self-tumor antigen enhances the immunogenicity of a pulsed dendritic cell vaccine. J Immunol. 2000;164(9):4797–803.PubMedCrossRefGoogle Scholar
  77. 77.
    Timmerman JM, Czerwinski DK, Davis TA, Hsu FJ, Benike C, Hao ZM, et al. Idiotype-pulsed dendritic cell vaccination for B-cell lymphoma: clinical and immune responses in 35 patients. Blood. 2002;99(5):1517–26.PubMedCrossRefGoogle Scholar
  78. 78.
    Millard AL, Ittelet D, Schooneman F, Bernard J. Dendritic cell KLH loading requirements for efficient CD4+ T-cell priming and help to peptide-specific cytotoxic T-cell response, in view of potential use in cancer vaccines. Vaccine. 2003;21(9–10):869–76.PubMedCrossRefGoogle Scholar
  79. 79.
    Shojaeian J, Jeddi-Tehrani M, Dokouhaki P, Mahmoudi AR, Ghods R, Bozorgmehr M, et al. Mutual helper effect in copulsing of dendritic cells with 2 antigens: a novel approach for improvement of dendritic-based vaccine efficacy against tumors and infectious diseases simultaneously. J Immunother. 2009;32(4):325–32.PubMedCrossRefGoogle Scholar
  80. 80.
    Lee JJ, Choi BH, Kang HK, Park MS, Park JS, Kim SK, et al. Induction of multiple myeloma-specific cytotoxic T lymphocyte stimulation by dendritic cell pulsing with purified and optimized myeloma cell lysates. Leuk Lymphoma. 2007;48(10):2022–31.PubMedCrossRefGoogle Scholar
  81. 81.
    Milazzo C, Reichardt VL, Muller MR, Grunebach F, Brossart P. Induction of myeloma-specific cytotoxic T cells using dendritic cells transfected with tumor-derived RNA. Blood. 2003;101(3):977–82.PubMedCrossRefGoogle Scholar
  82. 82.
    Qian J, Wang S, Yang J, Xie J, Lin P, Freeman ME III, et al. Targeting heat shock proteins for immunotherapy in multiple myeloma: generation of myeloma-specific CTLs using dendritic cells pulsed with tumor-derived gp96. Clin Cancer Res. 2005;11(24 Pt 1):8808–15.PubMedCrossRefGoogle Scholar
  83. 83.
    Gong J, Chen D, Kashiwaba M, Kufe D. Induction of antitumor activity by immunization with fusions of dendritic and carcinoma cells. Nat Med. 1997;3(5):558–61.PubMedCrossRefGoogle Scholar
  84. 84.
    Raje N, Hideshima T, Davies FE, Chauhan D, Treon SP, Young G, et al. Tumour cell/dendritic cell fusions as a vaccination strategy for multiple myeloma. Br J Haematol. 2004;125(3):343–52.PubMedCrossRefGoogle Scholar
  85. 85.
    Gong J, Koido S, Chen D, Tanaka Y, Huang L, Avigan D, et al. Immunization against murine multiple myeloma with fusions of dendritic and plasmacytoma cells is potentiated by interleukin 12. Blood. 2002;99(7):2512–7.PubMedCrossRefGoogle Scholar
  86. 86.
    Rosenblatt J, Vasir B, Uhl L, Blotta S, Macnamara C, Somaiya P, et al. Vaccination with dendritic cell/tumor fusion cells results in cellular and humoral antitumor immune responses in patients with multiple myeloma. Blood. 2011;117(2):393–402.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Jung ID, Shin SJ, Lee MG, Kang TH, Han HD, Lee SJ, et al. Enhancement of tumor-specific T cell-mediated immunity in dendritic cell-based vaccines by mycobacterium tuberculosis heat shock protein X. J Immunol. 2014;193(3):1233–45.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Kretz-Rommel A, Qin F, Dakappagari N, Torensma R, Faas S, Wu D, et al. In vivo targeting of antigens to human dendritic cells through DC-SIGN elicits stimulatory immune responses and inhibits tumor growth in grafted mouse models. J Immunother. 2007;30(7):715–26.PubMedCrossRefGoogle Scholar
  89. 89.
    Pereira CF, Torensma R, Hebeda K, Kretz-Rommel A, Faas SJ, Figdor CG, et al. In vivo targeting of DC-SIGN-positive antigen-presenting cells in a nonhuman primate model. J Immunother. 2007;30(7):705–14.PubMedCrossRefGoogle Scholar
  90. 90.
    Datta J, Terhune JH, Lowenfeld L, Cintolo JA, Xu S, Roses RE, et al. Optimizing dendritic cell-based approaches for cancer immunotherapy. Yale J Biol Med. 2014;87(4):491–518.PubMedPubMedCentralGoogle Scholar
  91. 91.
    Hawiger D, Inaba K, Dorsett Y, Guo M, Mahnke K, Rivera M, et al. Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J Exp Med. 2001;194(6):769–79.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Albert ML, Pearce SF, Francisco LM, Sauter B, Roy P, Silverstein RL, et al. Immature dendritic cells phagocytose apoptotic cells via alphavbeta5 and CD36, and cross-present antigens to cytotoxic T lymphocytes. J Exp Med. 1998;188(7):1359–68.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Albert ML, Sauter B, Bhardwaj N. Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature. 1998;392(6671):86–9.PubMedCrossRefGoogle Scholar
  94. 94.
    Heath WR, Carbone FR. Cross-presentation, dendritic cells, tolerance and immunity. Annu Rev Immunol. 2001;19:47–64.PubMedCrossRefGoogle Scholar
  95. 95.
    Jonuleit H, Giesecke-Tuettenberg A, Tuting T, Thurner-Schuler B, Stuge TB, Paragnik L, et al. A comparison of two types of dendritic cell as adjuvants for the induction of melanoma-specific T-cell responses in humans following intranodal injection. Int J Cancer. 2001;93(2):243–51.PubMedCrossRefGoogle Scholar
  96. 96.
    Bach JF. Regulatory T cells under scrutiny. Nat Rev Immunol. 2003;3(3):189–98.PubMedCrossRefGoogle Scholar
  97. 97.
    Jonuleit H, Schmitt E. The regulatory T cell family: distinct subsets and their interrelations. J Immunol. 2003;171(12):6323–7.PubMedCrossRefGoogle Scholar
  98. 98.
    Dhodapkar MV, Sznol M, Zhao B, Wang D, Carvajal RD, Keohan ML, et al. Induction of antigen-specific immunity with a vaccine targeting NY-ESO-1 to the dendritic cell receptor DEC-205. Sci Transl Med. 2014;6(232):232ra51.PubMedCrossRefGoogle Scholar
  99. 99.
    Bonifaz LC, Bonnyay DP, Charalambous A, Darguste DI, Fujii S, Soares H, et al. In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination. J Exp Med. 2004;199(6):815–24.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Mahnke K, Qian Y, Fondel S, Brueck J, Becker C, Enk AH. Targeting of antigens to activated dendritic cells in vivo cures metastatic melanoma in mice. Cancer Res. 2005;65(15):7007–12.PubMedCrossRefGoogle Scholar
  101. 101.
    Johnson TS, Mahnke K, Storn V, Schonfeld K, Ring S, Nettelbeck DM, et al. Inhibition of melanoma growth by targeting of antigen to dendritic cells via an anti-DEC-205 single-chain fragment variable molecule. Clin Cancer Res. 2008;14(24):8169–77.PubMedCrossRefGoogle Scholar
  102. 102.
    van Broekhoven CL, Parish CR, Demangel C, Britton WJ, Altin JG. Targeting dendritic cells with antigen-containing liposomes: a highly effective procedure for induction of antitumor immunity and for tumor immunotherapy. Cancer Res. 2004;64(12):4357–65.PubMedCrossRefGoogle Scholar
  103. 103.
    Wei H, Wang S, Zhang D, Hou S, Qian W, Li B, et al. Targeted delivery of tumor antigens to activated dendritic cells via CD11c molecules induces potent antitumor immunity in mice. Clin Cancer Res. 2009;15(14):4612–21.PubMedCrossRefGoogle Scholar
  104. 104.
    Sancho D, Mourao-Sa D, Joffre OP, Schulz O, Rogers NC, Pennington DJ, et al. Tumor therapy in mice via antigen targeting to a novel, DC-restricted C-type lectin. J Clin Invest. 2008;118(6):2098–110.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Dickgreber N, Stoitzner P, Bai Y, Price KM, Farrand KJ, Manning K, et al. Targeting antigen to MHC class II molecules promotes efficient cross-presentation and enhances immunotherapy. J Immunol. 2009;182(3):1260–9.PubMedCrossRefGoogle Scholar
  106. 106.
    Delneste Y, Magistrelli G, Gauchat J, Haeuw J, Aubry J, Nakamura K, et al. Involvement of LOX-1 in dendritic cell-mediated antigen cross-presentation. Immunity. 2002;17(3):353–62.PubMedCrossRefGoogle Scholar
  107. 107.
    He LZ, Crocker A, Lee J, Mendoza-Ramirez J, Wang XT, Vitale LA, et al. Antigenic targeting of the human mannose receptor induces tumor immunity. J Immunol. 2007;178(10):6259–67.PubMedCrossRefGoogle Scholar
  108. 108.
    Tagliani E, Guermonprez P, Sepulveda J, Lopez-Bravo M, Ardavin C, Amigorena S, et al. Selection of an antibody library identifies a pathway to induce immunity by targeting CD36 on steady-state CD8 alpha+ dendritic cells. J Immunol. 2008;180(5):3201–9.PubMedCrossRefGoogle Scholar
  109. 109.
    Loschko J, Schlitzer A, Dudziak D, Drexler I, Sandholzer N, Bourquin C, et al. Antigen delivery to plasmacytoid dendritic cells via BST2 induces protective T cell-mediated immunity. J Immunol. 2011;186(12):6718–25.PubMedCrossRefGoogle Scholar
  110. 110.
    Veinotte L, Gebremeskel S, Johnston B. CXCL16-positive dendritic cells enhance invariant natural killer T cell-dependent IFN-gamma production and tumor control. Oncoimmunology. 2016;5(6):e1160979.PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Santin AD, Hermonat PL, Ravaggi A, Bellone S, Cowan C, Coke C, et al. Development and therapeutic effect of adoptively transferred T cells primed by tumor lysate-pulsed autologous dendritic cells in a patient with metastatic endometrial cancer. Gynecol Obstet Invest. 2000;49(3):194–203.PubMedCrossRefGoogle Scholar
  112. 112.
    Liso A, Stockerl-Goldstein KE, Auffermann-Gretzinger S, Benike CJ, Reichardt V, van Beckhoven A, et al. Idiotype vaccination using dendritic cells after autologous peripheral blood progenitor cell transplantation for multiple myeloma. Biol Blood Marrow Transplant. 2000;6(6):621–7.PubMedCrossRefGoogle Scholar
  113. 113.
    Tjoa BA, Lodge PA, Salgaller ML, Boynton AL, Murphy GP. Dendritic cell-based immunotherapy for prostate cancer. CA Cancer J Clin. 1999;49(2):117–28, 65.PubMedCrossRefGoogle Scholar
  114. 114.
    Xu P, Tang S, Jiang L, Yang L, Zhang D, Feng S, et al. Nanomaterial-dependent immunoregulation of dendritic cells and its effects on biological activities of contraceptive nanovaccines. J Control Release. 2016;225:252–68.PubMedCrossRefGoogle Scholar
  115. 115.
    Ali OA, Emerich D, Dranoff G, Mooney DJ. In situ regulation of DC subsets and T cells mediates tumor regression in mice. Sci Transl Med. 2009;1(8):8ra19.PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Ali OA, Doherty E, Bell WJ, Fradet T, Hudak J, Laliberte MT, et al. Biomaterial-based vaccine induces regression of established intracranial glioma in rats. Pharm Res. 2011;28(5):1074–80.PubMedCrossRefGoogle Scholar
  117. 117.
    Hsu FJ, Benike C, Fagnoni F, Liles TM, Czerwinski D, Taidi B, et al. Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nat Med. 1996;2(1):52–8.PubMedCrossRefGoogle Scholar
  118. 118.
    Nestle FO, Alijagic S, Gilliet M, Sun Y, Grabbe S, Dummer R, et al. Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat Med. 1998;4(3):328–32.PubMedCrossRefGoogle Scholar
  119. 119.
    Thurner B, Haendle I, Roder C, Dieckmann D, Keikavoussi P, Jonuleit H, 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. 1999;190(11):1669–78.PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Mackensen A, Herbst B, Chen JL, Kohler G, Noppen C, Herr W, et al. Phase I study in melanoma patients of a vaccine with peptide-pulsed dendritic cells generated in vitro from CD34(+) hematopoietic progenitor cells. Int J Cancer. 2000;86(3):385–92.PubMedCrossRefGoogle Scholar
  121. 121.
    Kikuchi T, Akasaki Y, Irie M, Homma S, Abe T, Ohno T. Results of a phase I clinical trial of vaccination of glioma patients with fusions of dendritic and glioma cells. Cancer Immunol Immunother. 2001;50(7):337–44.PubMedCrossRefGoogle Scholar
  122. 122.
    Nair SK, Morse M, Boczkowski D, Cumming RI, Vasovic L, Gilboa E, et al. Induction of tumor-specific cytotoxic T lymphocytes in cancer patients by autologous tumor RNA-transfected dendritic cells. Ann Surg. 2002;235(4):540–9.PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Heiser A, Coleman D, Dannull J, Yancey D, Maurice MA, Lallas CD, et al. Autologous dendritic cells transfected with prostate-specific antigen RNA stimulate CTL responses against metastatic prostate tumors. J Clin Invest. 2002;109(3):409–17.PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Pecher G, Haring A, Kaiser L, Thiel E. Mucin gene (MUC1) transfected dendritic cells as vaccine: results of a phase I/II clinical trial. Cancer Immunol Immunother. 2002;51(11–12):669–73.PubMedCrossRefGoogle Scholar
  125. 125.
    Marten A, Renoth S, Heinicke T, Albers P, Pauli A, Mey U, et al. 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. 2003;14(5):483–94.PubMedCrossRefGoogle Scholar
  126. 126.
    Dannull J, Su Z, Rizzieri D, Yang BK, Coleman D, Yancey D, et al. Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J Clin Invest. 2005;115(12):3623–33.PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Salcedo M, Bercovici N, Taylor R, Vereecken P, Massicard S, Duriau D, et al. Vaccination of melanoma patients using dendritic cells loaded with an allogeneic tumor cell lysate. Cancer Immunol Immunother. 2006;55(7):819–29.PubMedCrossRefGoogle Scholar
  128. 128.
    Palucka AK, Ueno H, Connolly J, Kerneis-Norvell F, Blanck JP, Johnston DA, et al. Dendritic cells loaded with killed allogeneic melanoma cells can induce objective clinical responses and MART-1 specific CD8+ T-cell immunity. J Immunother. 2006;29(5):545–57.PubMedCrossRefGoogle Scholar
  129. 129.
    Okada H, Kalinski P, Ueda R, Hoji A, Kohanbash G, Donegan TE, et al. Induction of CD8+ T-cell responses against novel glioma-associated antigen peptides and clinical activity by vaccinations with {alpha}-type 1 polarized dendritic cells and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in patients with recurrent malignant glioma. J Clin Oncol. 2011;29(3):330–6.PubMedCrossRefGoogle Scholar
  130. 130.
    Romano E, Rossi M, Ratzinger G, de Cos MA, Chung DJ, Panageas KS, et al. Peptide-loaded Langerhans cells, despite increased IL15 secretion and T-cell activation in vitro, elicit antitumor T-cell responses comparable to peptide-loaded monocyte-derived dendritic cells in vivo. Clin Cancer Res. 2011;17(7):1984–97.PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Kandalaft LE, Powell DJ Jr, Chiang CL, Tanyi J, Kim S, Bosch M, et al. Autologous lysate-pulsed dendritic cell vaccination followed by adoptive transfer of vaccine-primed ex vivo co-stimulated T cells in recurrent ovarian cancer. Oncoimmunology. 2013;2(1):e22664.PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Rosenblatt J, Avivi I, Vasir B, Uhl L, Munshi NC, Katz T, et al. Vaccination with dendritic cell/tumor fusions following autologous stem cell transplant induces immunologic and clinical responses in multiple myeloma patients. Clin Cancer Res. 2013;19(13):3640–8.PubMedPubMedCentralCrossRefGoogle Scholar
  133. 133.
    Mitchell DA, Batich KA, Gunn MD, Huang MN, Sanchez-Perez L, Nair SK, et al. Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients. Nature. 2015;519(7543):366–9.PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    Son YI, Mailliard RB, Watkins SC, Lotze MT. Dendritic cells pulsed with apoptotic squamous cell carcinoma have anti-tumor effects when combined with interleukin-2. Laryngoscope. 2001;111(8):1472–8.PubMedCrossRefGoogle Scholar
  135. 135.
    Shimizu K, Fields RC, Giedlin M, Mule JJ. Systemic administration of interleukin 2 enhances the therapeutic efficacy of dendritic cell-based tumor vaccines. Proc Natl Acad Sci U S A. 1999;96(5):2268–73.PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Tong Y, Song W, Crystal RG. Combined intratumoral injection of bone marrow-derived dendritic cells and systemic chemotherapy to treat pre-existing murine tumors. Cancer Res. 2001;61(20):7530–5.PubMedGoogle Scholar
  137. 137.
    Swaika A, Hammond WA, Joseph RW. Current state of anti-PD-L1 and anti-PD-1 agents in cancer therapy. Mol Immunol. 2015;67(2 Pt A):4–17.PubMedCrossRefGoogle Scholar
  138. 138.
    Heckelsmiller K, Beck S, Rall K, Sipos B, Schlamp A, Tuma E, et al. Combined dendritic cell- and CpG oligonucleotide-based immune therapy cures large murine tumors that resist chemotherapy. Eur J Immunol. 2002;32(11):3235–45.PubMedCrossRefGoogle Scholar
  139. 139.
    Prins RM, Wang X, Soto H, Young E, Lisiero DN, Fong B, et al. Comparison of glioma-associated antigen peptide-loaded versus autologous tumor lysate-loaded dendritic cell vaccination in malignant glioma patients. J Immunother. 2013;36(2):152–7.PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    Hasumi K, Aoki Y, Watanabe R, Hankey KG, Mann DL. Therapeutic response in patients with advanced malignancies treated with combined dendritic cell-activated T cell based immunotherapy and intensity-modulated radiotherapy. Cancers (Basel). 2011;3(2):2223–42.CrossRefGoogle Scholar
  141. 141.
    Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363(5):411–22.PubMedCrossRefGoogle Scholar
  142. 142.
    McNeel DG, Gardner TA, Higano CS, Kantoff PW, Small EJ, Wener MH, et al. A transient increase in eosinophils is associated with prolonged survival in men with metastatic castration-resistant prostate cancer who receive sipuleucel-T. Cancer Immunol Res. 2014;2(10):988–99.PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Small EJ, Higano CS, Kantoff PW, Whitmore JB, Frohlich MW, Petrylak DP. Time to disease-related pain and first opioid use in patients with metastatic castration-resistant prostate cancer treated with sipuleucel-T. Prostate Cancer Prostatic Dis. 2014;17(3):259–64.PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    Holtl L, Rieser C, Papesh C, Ramoner R, Herold M, Klocker H, et al. Cellular and humoral immune responses in patients with metastatic renal cell carcinoma after vaccination with antigen pulsed dendritic cells. J Urol. 1999;161(3):777–82.PubMedCrossRefGoogle Scholar
  145. 145.
    Dhodapkar MV, Steinman RM, Sapp M, Desai H, Fossella C, Krasovsky J, et al. Rapid generation of broad T-cell immunity in humans after a single injection of mature dendritic cells. J Clin Invest. 1999;104(2):173–80.PubMedPubMedCentralCrossRefGoogle Scholar
  146. 146.
    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(2):233–8.PubMedPubMedCentralCrossRefGoogle Scholar
  147. 147.
    Dhodapkar MV, Steinman RM. Antigen-bearing immature dendritic cells induce peptide-specific CD8(+) regulatory T cells in vivo in humans. Blood. 2002;100(1):174–7.PubMedCrossRefGoogle Scholar
  148. 148.
    Schuler-Thurner B, Schultz ES, Berger TG, Weinlich G, Ebner S, Woerl P, et al. Rapid induction of tumor-specific type 1 T helper cells in metastatic melanoma patients by vaccination with mature, cryopreserved, peptide-loaded monocyte-derived dendritic cells. J Exp Med. 2002;195(10):1279–88.PubMedPubMedCentralCrossRefGoogle Scholar
  149. 149.
    Fong L, Hou Y, Rivas A, Benike C, Yuen A, Fisher GA, et al. Altered peptide ligand vaccination with Flt3 ligand expanded dendritic cells for tumor immunotherapy. Proc Natl Acad Sci U S A. 2001;98(15):8809–14.PubMedPubMedCentralCrossRefGoogle Scholar
  150. 150.
    Fong L, Brockstedt D, Benike C, Breen JK, Strang G, Ruegg CL, et al. Dendritic cell-based xenoantigen vaccination for prostate cancer immunotherapy. J Immunol. 2001;167(12):7150–6.PubMedCrossRefGoogle Scholar
  151. 151.
    Fong L, Brockstedt D, Benike C, Wu L, Engleman EG. Dendritic cells injected via different routes induce immunity in cancer patients. J Immunol. 2001;166(6):4254–9.PubMedCrossRefGoogle Scholar
  152. 152.
    Escudier B, Dorval T, Chaput N, Andre F, Caby MP, Novault S, et al. Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of the first phase I clinical trial. J Transl Med. 2005;3(1):10.PubMedPubMedCentralCrossRefGoogle Scholar
  153. 153.
    Holtl L, Ramoner R, Zelle-Rieser C, Gander H, Putz T, Papesh C, et al. Allogeneic dendritic cell vaccination against metastatic renal cell carcinoma with or without cyclophosphamide. Cancer Immunol Immunother. 2005;54(7):663–70.PubMedCrossRefGoogle Scholar
  154. 154.
    Banchereau J, Ueno H, Dhodapkar M, Connolly J, Finholt JP, Klechevsky E, et al. Immune and clinical outcomes in patients with stage IV melanoma vaccinated with peptide-pulsed dendritic cells derived from CD34+ progenitors and activated with type I interferon. J Immunother. 2005;28(5):505–16.PubMedCrossRefGoogle Scholar
  155. 155.
    Hildenbrand B, Sauer B, Kalis O, Stoll C, Freudenberg MA, Niedermann G, et al. Immunotherapy of patients with hormone-refractory prostate carcinoma pre-treated with interferon-gamma and vaccinated with autologous PSA-peptide loaded dendritic cells--a pilot study. Prostate. 2007;67(5):500–8.PubMedCrossRefGoogle Scholar
  156. 156.
    Poschke I, Mao Y, Adamson L, Salazar-Onfray F, Masucci G, Kiessling R. Myeloid-derived suppressor cells impair the quality of dendritic cell vaccines. Cancer Immunol Immunother. 2012;61(6):827–38.PubMedCrossRefGoogle Scholar
  157. 157.
    Galluzzi L, Senovilla L, Vacchelli E, Eggermont A, Fridman WH, Galon J, et al. Trial watch: dendritic cell-based interventions for cancer therapy. Oncoimmunology. 2012;1(7):1111–34.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Shah Md. Shahjahan Miah
    • 1
  • Timothy K. Erick
    • 1
  • Dwaine F. Emerich
    • 2
    Email author
  1. 1.Department of Microbiology and ImmunologyBrown UniversityProvidenceUSA
  2. 2.VP Research and DevelopmentNsGene, Inc.ProvidenceUSA

Personalised recommendations