Antitumor dendritic cell–based vaccines: lessons from 20 years of clinical trials and future perspectives

Translational Research

Volumn 168, Issue , 2016, Pages 74-95

  Constantino, João ^a   Gomes, Célia ^b,c   Falcão, Amílcar ^a,c   Cruz, Maria T ^a,c   Neves, Bruno M ^a,c,d  

^a UNIVERSITY OF COIMBRA   (Portugal)

^b UNIVERSITY OF COIMBRA   (Portugal)

^c UNIVERSITY OF COIMBRA   (Portugal)

^d UNIVERSITY OF AVEIRO   (Portugal)

Author keywords

[No Author keywords available]

Indexed keywords

CANCER VACCINE; DENDRITIC CELL VACCINE; TUMOR ANTIGEN;

CANCER IMMUNIZATION; CELL INTERACTION; CELL MANIPULATION; CELL MATURATION; DENDRITIC CELL; DRUG TARGETING; EX VIVO STUDY; HUMAN; IMMUNOBIOLOGY; IN VIVO STUDY; META ANALYSIS (TOPIC); NEOPLASM; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SYSTEMATIC REVIEW (TOPIC); T LYMPHOCYTE; VACCINE PRODUCTION; ANIMAL; IMMUNOLOGY; NEOPLASMS;

ANIMALS; CANCER VACCINES; DENDRITIC CELLS; HUMANS; NEOPLASMS;

EID: 84940068714     PISSN: 19315244     EISSN: 18781810     Source Type: Journal    
DOI: 10.1016/j.trsl.2015.07.008     Document Type: Review

References (167)

1. 1 Steinman, R.M., Cohn, Z.A., Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J Exp Med 137 (1973), 1142–1162 Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2139237&tool=pmcentrez&rendertype=abstract Accessed May 8, 2015.
2. 2 Steinman, R.M., Banchereau, J., Taking dendritic cells into medicine. Nature 449 (2007), 419–426.
3. 3 Mukherji, B., Chakraborty, N.G., Yamasaki, S., et al. Induction of antigen-specific cytolytic T cells in situ in human melanoma by immunization with synthetic peptide-pulsed autologous antigen presenting cells. Proc Natl Acad Sci U S A 92 (1995), 8078–8082 Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=41290&tool=pmcentrez&rendertype=abstract Accessed May 8, 2015.
4. 4 Anguille, S., Smits, E.L., Lion, E., van Tendeloo, V.F., Berneman, Z.N., Clinical use of dendritic cells for cancer therapy. Lancet Oncol 15 (2014), e257–e267.
5. 5 Madan, R.A., Gulley, J.L., Fojo, T., Dahut, W.L., Therapeutic cancer vaccines in prostate cancer: the paradox of improved survival without changes in time to progression. Oncologist 15 (2010), 969–975.
6. 6 Kantoff, P.W., Higano, C.S., Shore, N.D., et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 363 (2010), 411–422.
7. 7 Poltorak, M.P., Schraml, B.U., Fate mapping of dendritic cells. Front Immunol, 6, 2015, 199.
8. 8 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 31 (2013), 563–604.
9. 9 Naik, S.H., Demystifying the development of dendritic cell subtypes, a little. Immunol Cell Biol 86 (2008), 439–452.
10. 10 Guilliams, M., Ginhoux, F., Jakubzick, C., et al. Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny. Nat Rev Immunol 14 (2014), 571–578.
11. 11 Malissen, B., Tamoutounour, S., Henri, S., The origins and functions of dendritic cells and macrophages in the skin. Nat Rev Immunol 14 (2014), 417–428.
12. 12 Bachem, A., Güttler, S., Hartung, E., et al. Superior antigen cross-presentation and XCR1 expression define human CD11c+CD141+ cells as homologues of mouse CD8+ dendritic cells. J Exp Med 207 (2010), 1273–1281.
13. 13 Jongbloed, S.L., Kassianos, A.J., McDonald, K.J., et al. Human CD141+ (BDCA-3)+ dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens. J Exp Med 207 (2010), 1247–1260.
14. 14 Haniffa, M., Shin, A., Bigley, V., et al. Human tissues contain CD141hi cross-presenting dendritic cells with functional homology to mouse CD103+ nonlymphoid dendritic cells. Immunity 37 (2012), 60–73.
15. 15 Kanitakis, J., Morelon, E., Petruzzo, P., Badet, L., Dubernard, J.-M., Self-renewal capacity of human epidermal Langerhans cells: observations made on a composite tissue allograft. Exp Dermatol 20 (2011), 145–146.
16. 16 Geijtenbeek, T.B.H., Gringhuis, S.I., Signalling through C-type lectin receptors: shaping immune responses. Nat Rev Immunol 9 (2009), 465–479.
17. 17 Van Vliet, S.J., García-Vallejo, J.J., van Kooyk, Y., Dendritic cells and C-type lectin receptors: coupling innate to adaptive immune responses. Immunol Cell Biol 86 (2008), 580–587.
18. 18 Schlitzer, A., Ginhoux, F., Organization of the mouse and human DC network. Curr Opin Immunol 26 (2014), 90–99.
19. 19 Dzionek, A., Fuchs, A., Schmidt, P., et al. BDCA-2, BDCA-3, and BDCA-4: three markers for distinct subsets of dendritic cells in human peripheral blood. J Immunol 165 (2000), 6037–6046.
20. 20 Hoeffel, G., Ripoche, A.-C., Matheoud, D., et al. Antigen crosspresentation by human plasmacytoid dendritic cells. Immunity 27 (2007), 481–492.
21. 21 Vyas, J.M., Van der Veen, A.G., Ploegh, H.L., The known unknowns of antigen processing and presentation. Nat Rev Immunol 8 (2008), 607–618.
22. 22 Adams, E.J., Lipid presentation by human CD1 molecules and the diverse T cell populations that respond to them. Curr Opin Immunol 26 (2014), 1–6.
23. 23 Amigorena, S., Savina, A., Intracellular mechanisms of antigen cross presentation in dendritic cells. Curr Opin Immunol 22 (2010), 109–117.
24. 24 Banchereau, J., Briere, F., Caux, C., et al. Immunobiology of dendritic cells. Annu Rev Immunol 18 (2000), 767–811.
25. 25 Randolph, G.J., Ochando, J., Partida-Sánchez, S., Migration of dendritic cell subsets and their precursors. Annu Rev Immunol 26 (2008), 293–316.
26. 26 Blanco, P., Palucka, A.K., Pascual, V., Banchereau, J., Dendritic cells and cytokines in human inflammatory and autoimmune diseases. Cytokine Growth Factor Rev 19 (2008), 41–52.
27. 27 Lukacs-Kornek, V., Engel, D., Tacke, F., Kurts, C., The role of chemokines and their receptors in dendritic cell biology. Front Biosci 13 (2008), 2238–2252 Available at: http://www.ncbi.nlm.nih.gov/pubmed/17981706 Accessed June 25, 2015.
28. 28 Reis e Sousa, C., Dendritic cells in a mature age. Nat Rev Immunol 6 (2006), 476–483.
29. 29 Tan, J.K.H., O'Neill, H.C., Maturation requirements for dendritic cells in T cell stimulation leading to tolerance versus immunity. J Leukoc Biol 78 (2005), 319–324.
30. 30 Bour-Jordan, H., Bluestone, J.A., Regulating the regulators: costimulatory signals control the homeostasis and function of regulatory T cells. Immunol Rev 229 (2009), 41–66.
31. 31 Redmond, W.L., Ruby, C.E., Weinberg, A.D., The role of OX40-mediated co-stimulation in T-cell activation and survival. Crit Rev Immunol 29 (2009), 187–201 Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3180959&tool=pmcentrez&rendertype=abstract Accessed June 25, 2015.
32. 32 Hippen, K.L., Harker-Murray, P., Porter, S.B., et al. Umbilical cord blood regulatory T-cell expansion and functional effects of tumor necrosis factor receptor family members OX40 and 4-1BB expressed on artificial antigen-presenting cells. Blood 112 (2008), 2847–2857.
33. 33 Curtsinger, J.M., Johnson, C.M., Mescher, M.F., CD8 T cell clonal expansion and development of effector function require prolonged exposure to antigen, costimulation, and signal 3 cytokine. J Immunol 171 (2003), 5165–5171 Available at: http://www.ncbi.nlm.nih.gov/pubmed/14607916 Accessed June 25, 2015.
34. 34 Kaiko, G.E., Horvat, J.C., Beagley, K.W., Hansbro, P.M., Immunological decision-making: how does the immune system decide to mount a helper T-cell response?. Immunology 123 (2008), 326–338.
35. 35 Kastenmuller, W., Gasteiger, G., Subramanian, N., et al. Regulatory T cells selectively control CD8+ T cell effector pool size via IL-2 restriction. J Immunol 187 (2011), 3186–3197.
36. 36 Williams, M.A., Bevan, M.J., Effector and memory CTL differentiation. Annu Rev Immunol 25 (2007), 171–192.
37. 37 Pearce, E.L., Shen, H., Generation of CD8 T cell memory is regulated by IL-12. J Immunol 179 (2007), 2074–2081 Available at: http://www.ncbi.nlm.nih.gov/pubmed/17675465 Accessed May 17, 2015.
38. 38 Josefowicz, S.Z., Lu, L.-F., Rudensky, A.Y., Regulatory T cells: mechanisms of differentiation and function. Annu Rev Immunol 30 (2012), 531–564.
39. 39 Melief, C.J., Kast, W.M., Cytotoxic T lymphocyte therapy of cancer and tumor escape mechanisms. Semin Cancer Biol 2 (1991), 347–354 Available at: http://www.ncbi.nlm.nih.gov/pubmed/1773050 Accessed May 8, 2015.
40. 40 Hariharan, K., Braslawsky, G., Black, A., Raychaudhuri, S., Hanna, N., The induction of cytotoxic T cells and tumor regression by soluble antigen formulation. Cancer Res 55 (1995), 3486–3489 Available at: http://www.ncbi.nlm.nih.gov/pubmed/7627951 Accessed May 8, 2015.
41. 41 Appay, V., Douek, D.C., Price, D.A., CD8+ T cell efficacy in vaccination and disease. Nat Med 14 (2008), 623–628.
42. 42 Zhang, N., Bevan, M.J., CD8(+) T cells: foot soldiers of the immune system. Immunity 35 (2011), 161–168.
43. 43 Quezada, S.A., Peggs, K.S., Exploiting CTLA-4, PD-1 and PD-L1 to reactivate the host immune response against cancer. Br J Cancer 108 (2013), 1560–1565.
44. 44 Haabeth, O.A.W., Tveita, A.A., Fauskanger, M., et al. How Do CD4(+) T cells detect and eliminate tumor cells that either lack or express MHC class II molecules?. Front Immunol, 5, 2014, 174.
45. 45 Spolski, R., Leonard, W.J., Interleukin-21: a double-edged sword with therapeutic potential. Nat Rev Drug Discov 13 (2014), 379–395.
46. 46 Antony, P.A., Piccirillo, C.A., Akpinarli, A., et al. CD8+ T cell immunity against a tumor/self-antigen is augmented by CD4+ T helper cells and hindered by naturally occurring T regulatory cells. J Immunol 174 (2005), 2591–2601 Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1403291&tool=pmcentrez&rendertype=abstract Accessed May 8, 2015.
47. 47 Sun, J.C., Bevan, M.J., Defective CD8 T cell memory following acute infection without CD4 T cell help. Science 300 (2003), 339–342.
48. 48 Larsen, S.K., Gao, Y., Basse, P.H., NK cells in the tumor microenvironment. Crit Rev Oncog 19 (2014), 91–105 Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4062922&tool=pmcentrez&rendertype=abstract Accessed May 8, 2015.
49. 49 Cheng, M., Chen, Y., Xiao, W., Sun, R., Tian, Z., NK cell-based immunotherapy for malignant diseases. Cell Mol Immunol 10 (2013), 230–252.
50. 50 Hayakawa, Y., Screpanti, V., Yagita, H., et al. NK cell TRAIL eliminates immature dendritic cells in vivo and limits dendritic cell vaccination efficacy. J Immunol 172 (2004), 123–129 Available at: http://www.ncbi.nlm.nih.gov/pubmed/14688317 Accessed May 8, 2015.
51. 51 Pampena, M.B., Levy, E.M., Natural killer cells as helper cells in dendritic cell cancer vaccines. Front Immunol, 6, 2015, 13.
52. 52 Zou, W., Chen, L., Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol 8 (2008), 467–477.
53. 53 Sasaki, K., Pardee, A.D., Okada, H., Storkus, W.J., IL-4 inhibits VLA-4 expression on Tc1 cells resulting in poor tumor infiltration and reduced therapy benefit. Eur J Immunol 38 (2008), 2865–2873.
54. 54 Chen, M.-L., Pittet, M.J., Gorelik, L., et al. Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-beta signals in vivo. Proc Natl Acad Sci U S A 102 (2005), 419–424.
55. 55 Jarnicki, A.G., Lysaght, J., Todryk, S., Mills, K.H.G., Suppression of antitumor immunity by IL-10 and TGF-beta-producing T cells infiltrating the growing tumor: influence of tumor environment on the induction of CD4+ and CD8+ regulatory T cells. J Immunol 177 (2006), 896–904 Available at: http://www.ncbi.nlm.nih.gov/pubmed/16818744 Accessed May 9, 2015.
56. 56 McNally, A., Hill, G.R., Sparwasser, T., Thomas, R., Steptoe, R.J., CD4+CD25+ regulatory T cells control CD8+ T-cell effector differentiation by modulating IL-2 homeostasis. Proc Natl Acad Sci U S A 108 (2011), 7529–7534.
57. 57 Draube, A., Klein-González, N., Mattheus, S., et al. Dendritic cell based tumor vaccination in prostate and renal cell cancer: a systematic review and meta-analysis. PLoS One, 6, 2011, e18801.
58. 58 Fernandez, N.C., Lozier, A., Flament, C., et al. Dendritic cells directly trigger NK cell functions: cross-talk relevant in innate anti-tumor immune responses in vivo. Nat Med 5 (1999), 405–411.
59. 59 Lion, E., Smits, E.L.J.M., Berneman, Z.N., Van Tendeloo, V.F.I., NK cells: key to success of DC-based cancer vaccines?. Oncologist 17 (2012), 1256–1270.
60. 60 Boudreau, J.E., Bridle, B.W., Stephenson, K.B., et al. Recombinant vesicular stomatitis virus transduction of dendritic cells enhances their ability to prime innate and adaptive antitumor immunity. Mol Ther 17 (2009), 1465–1472.
61. 61 Bouwer, A.L., Saunderson, S.C., Caldwell, F.J., et al. NK cells are required for dendritic cell-based immunotherapy at the time of tumor challenge. J Immunol 192 (2014), 2514–2521.
62. 62 Makkouk, A., Weiner, G.J., Cancer immunotherapy and breaking immune tolerance: new approaches to an old challenge. Cancer Res 75 (2015), 5–10.
63. 63 Aarntzen, E.H.J.G., De Vries, I.J.M., Lesterhuis, W.J., et al. Targeting CD4(+) T-helper cells improves the induction of antitumor responses in dendritic cell-based vaccination. Cancer Res 73 (2013), 19–29.
64. 64 Schreibelt, G., Bol, K.F., Aarntzen, E.H., et al. Importance of helper T-cell activation in dendritic cell-based anticancer immunotherapy. Oncoimmunology, 2, 2013, e24440.
65. 65 Kalinski, P., Dendritic cells in immunotherapy of established cancer: roles of signals 1, 2, 3 and 4. Curr Opin Investig Drugs 10 (2009), 526–535 Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2919813&tool=pmcentrez&rendertype=abstract Accessed June 26, 2015.
66. 66 Westermann, J., Körner, I.J., Kopp, J., et al. Cryopreservation of mature monocyte-derived human dendritic cells for vaccination: influence on phenotype and functional properties. Cancer Immunol Immunother 52 (2003), 194–198.
67. 67 Flörcken, A., Kopp, J., van Lessen, A., et al. Allogeneic partially HLA-matched dendritic cells pulsed with autologous tumor cell lysate as a vaccine in metastatic renal cell cancer: a clinical phase I/II study. Hum Vaccin Immunother 9 (2013), 1217–1227.
68. 68 Hus, I., Roliński, J., Tabarkiewicz, J., et al. Allogeneic dendritic cells pulsed with tumor lysates or apoptotic bodies as immunotherapy for patients with early-stage B-cell chronic lymphocytic leukemia. Leukemia 19 (2005), 1621–1627.
69. 69 Gabrilovich, D., Mechanisms and functional significance of tumour-induced dendritic-cell defects. Nat Rev Immunol 4 (2004), 941–952.
70. 70 Pinzon-Charry, A., Maxwell, T., López, J.A., Dendritic cell dysfunction in cancer: a mechanism for immunosuppression. Immunol Cell Biol 83 (2005), 451–461.
71. 71 Orsini, E., Guarini, A., Chiaretti, S., Mauro, F.R., Foa, R., The circulating dendritic cell compartment in patients with chronic lymphocytic leukemia is severely defective and unable to stimulate an effective T-cell response. Cancer Res 63 (2003), 4497–4506 Available at: http://www.ncbi.nlm.nih.gov/pubmed/12907623 Accessed May 9, 2015.
72. 72 Della Bella, S., Gennaro, M., Vaccari, M., et al. Altered maturation of peripheral blood dendritic cells in patients with breast cancer. Br J Cancer 89 (2003), 1463–1472.
73. 73 Toriyama, K., Wen, D.R., Paul, E., Cochran, A.J., Variations in the distribution, frequency, and phenotype of Langerhans cells during the evolution of malignant melanoma of the skin. J Invest Dermatol 100 (1993), 269S–273S Available at: http://www.ncbi.nlm.nih.gov/pubmed/7680054 Accessed June 26, 2015.
74. 74 Troy, A.J., Summers, K.L., Davidson, P.J., Atkinson, C.H., Hart, D.N., Minimal recruitment and activation of dendritic cells within renal cell carcinoma. Clin Cancer Res 4 (1998), 585–593 Available at: http://www.ncbi.nlm.nih.gov/pubmed/9533525 Accessed June 26, 2015.
75. 75 Ratzinger, G., Baggers, J., de Cos, M.A., et al. Mature human Langerhans cells derived from CD34+ hematopoietic progenitors stimulate greater cytolytic T lymphocyte activity in the absence of bioactive IL-12p70, by either single peptide presentation or cross-priming, than do dermal-interstitial or monoc. J Immunol 173 (2004), 2780–2791 Available at: http://www.ncbi.nlm.nih.gov/pubmed/15294997 Accessed May 9, 2015.
76. 76 Romano, E., Rossi, M., Ratzinger, G., 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 17 (2011), 1984–1997.
77. 77 Tel, J., Aarntzen, E.H.J.G., Baba, T., et al. Natural human plasmacytoid dendritic cells induce antigen-specific T-cell responses in melanoma patients. Cancer Res 73 (2013), 1063–1075.
78. 78 Schnurr, M., Chen, Q., Shin, A., et al. Tumor antigen processing and presentation depend critically on dendritic cell type and the mode of antigen delivery. Blood 105 (2005), 2465–2472.
79. 79 Kroemer, G., Zitvogel, L., Can the exome and the immunome converge on the design of efficient cancer vaccines?. Oncoimmunology 1 (2012), 579–580.
80. 80 Seremet, T., Brasseur, F., Coulie, P.G., Tumor-specific antigens and immunologic adjuvants in cancer immunotherapy. Cancer J 17 (2011), 325–330.
81. 81 Galluzzi, L., Senovilla, L., Vacchelli, E., et al. Trial watch: dendritic cell-based interventions for cancer therapy. Oncoimmunology 1 (2012), 1111–1134.
82. 82 Albert, M.L., Pearce, S.F., Francisco, L.M., et al. Immature dendritic cells phagocytose apoptotic cells via alphavbeta5 and CD36, and cross-present antigens to cytotoxic T lymphocytes. J Exp Med 188 (1998), 1359–1368 Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2212488&tool=pmcentrez&rendertype=abstract Accessed May 9, 2015.
83. 83 Kokhaei, P., Choudhury, A., Mahdian, R., et al. Apoptotic tumor cells are superior to tumor cell lysate, and tumor cell RNA in induction of autologous T cell response in B-CLL. Leukemia 18 (2004), 1810–1815.
84. 84 Zappasodi, R., Pupa, S.M., Ghedini, G.C., et al. Improved clinical outcome in indolent B-cell lymphoma patients vaccinated with autologous tumor cells experiencing immunogenic death. Cancer Res 70 (2010), 9062–9072.
85. 85 Boczkowski, D., Nair, S.K., Snyder, D., Gilboa, E., Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo. J Exp Med 184 (1996), 465–472 Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2192710&tool=pmcentrez&rendertype=abstract Accessed May 9, 2015.
86. 86 Bonehill, A., Van Nuffel, A.M.T., Corthals, J., et al. Single-step antigen loading and activation of dendritic cells by mRNA electroporation for the purpose of therapeutic vaccination in melanoma patients. Clin Cancer Res 15 (2009), 3366–3375.
87. 87 Wilgenhof, S., Van Nuffel, A.M.T., Corthals, J., et al. Therapeutic vaccination with an autologous mRNA electroporated dendritic cell vaccine in patients with advanced melanoma. J Immunother 34 (2011), 448–456.
88. 88 Benteyn, D., Van Nuffel, A.M.T., Wilgenhof, S., et al. Characterization of CD8+ T-cell responses in the peripheral blood and skin injection sites of melanoma patients treated with mRNA electroporated autologous dendritic cells (TriMixDC-MEL). Biomed Res Int, 2013, 2013, 976383.
89. 89 Van Nuffel, A.M.T., Benteyn, D., Wilgenhof, S., et al. Dendritic cells loaded with mRNA encoding full-length tumor antigens prime CD4+ and CD8+ T cells in melanoma patients. Mol Ther 20 (2012), 1063–1074.
90. 90 Gilboa, E., Vieweg, J., Cancer immunotherapy with mRNA-transfected dendritic cells. Immunol Rev 199 (2004), 251–263.
91. 91 Di Nicola, M., Carlo-Stella, C., Mortarini, R., et al. Boosting T cell-mediated immunity to tyrosinase by vaccinia virus-transduced, CD34(+)-derived dendritic cell vaccination: a phase I trial in metastatic melanoma. Clin Cancer Res 10 (2004), 5381–5390.
92. 92 Steele, J.C., Rao, A., Marsden, J.R., et al. Phase I/II trial of a dendritic cell vaccine transfected with DNA encoding melan A and gp100 for patients with metastatic melanoma. Gene Ther 18 (2011), 584–593.
93. 93 Butterfield, L.H., Comin-Anduix, B., Vujanovic, L., et al. Adenovirus MART-1-engineered autologous dendritic cell vaccine for metastatic melanoma. J Immunother 31 (2008), 294–309.
94. 94 Humrich, J., Jenne, L., Viral vectors for dendritic cell-based immunotherapy. Curr Top Microbiol Immunol 276 (2003), 241–259 Available at: http://www.ncbi.nlm.nih.gov/pubmed/12797451 Accessed July 5, 2015.
95. 95 Wang, H., Zhang, L., Kung, S.K.P., Emerging applications of lentiviral vectors in dendritic cell-based immunotherapy. Immunotherapy 2 (2010), 685–695.
96. 96 Wang, J., Saffold, S., Cao, X., Krauss, J., Chen, W., Eliciting T cell immunity against poorly immunogenic tumors by immunization with dendritic cell-tumor fusion vaccines. J Immunol 161 (1998), 5516–5524 Available at: http://www.ncbi.nlm.nih.gov/pubmed/9820528 Accessed May 9, 2015.
97. 97 Vasir, B., Wu, Z., Crawford, K., et al. Fusions of dendritic cells with breast carcinoma stimulate the expansion of regulatory T cells while concomitant exposure to IL-12, CpG oligodeoxynucleotides, and anti-CD3/CD28 promotes the expansion of activated tumor reactive cells. J Immunol 181 (2008), 808–821 Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2938172&tool=pmcentrez&rendertype=abstract Accessed May 9, 2015.
98. 98 Rosenblatt, J., Glotzbecker, B., Mills, H., et al. PD-1 blockade by CT-011, anti-PD-1 antibody, enhances ex vivo T-cell responses to autologous dendritic cell/myeloma fusion vaccine. J Immunother 34 (2011), 409–418.
99. 99 Kokhaei, P., Rezvany, M.R., Virving, L., et al. Dendritic cells loaded with apoptotic tumour cells induce a stronger T-cell response than dendritic cell-tumour hybrids in B-CLL. Leukemia 17 (2003), 894–899.
100. 100 De Vries, I.J.M., Lesterhuis, W.J., Scharenborg, N.M., et al. Maturation of dendritic cells is a prerequisite for inducing immune responses in advanced melanoma patients. Clin Cancer Res 9 (2003), 5091–5100 Available at: http://www.ncbi.nlm.nih.gov/pubmed/14613986 Accessed May 9, 2015.
101. 101 Dhodapkar, M.V., Steinman, R.M., 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 193 (2001), 233–238 Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2193335&tool=pmcentrez&rendertype=abstract Accessed May 9, 2015.
102. 102 Okada, H., Kalinski, P., Ueda, R., 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. J Clin Oncol 29 (2011), 330–336.
103. 103 Carreno, B.M., Becker-Hapak, M., Huang, A., et al. IL-12p70-producing patient DC vaccine elicits Tc1-polarized immunity. J Clin Invest 123 (2013), 3383–3394.
104. 104 Okada, N., Mori, N., Koretomo, R., et al. Augmentation of the migratory ability of DC-based vaccine into regional lymph nodes by efficient CCR7 gene transduction. Gene Ther 12 (2005), 129–139.
105. 105 González, F.E., Ortiz, C., Reyes, M., et al. Melanoma cell lysate induces CCR7 expression and in vivo migration to draining lymph nodes of therapeutic human dendritic cells. Immunology 142 (2014), 396–405.
106. 106 Scandella, E., Men, Y., Gillessen, S., Förster, R., Groettrup, M., Prostaglandin E2 is a key factor for CCR7 surface expression and migration of monocyte-derived dendritic cells. Blood 100 (2002), 1354–1361.
107. 107 Jongmans, W., Tiemessen, D.M., van Vlodrop, I.J.H., Mulders, P.F.A., Oosterwijk, E., Th1-polarizing capacity of clinical-grade dendritic cells is triggered by Ribomunyl but is compromised by PGE2: the importance of maturation cocktails. J Immunother 28 (2005), 480–487 Available at: http://www.ncbi.nlm.nih.gov/pubmed/16113604 Accessed May 9, 2015.
108. 108 Boullart, A.C.I., Aarntzen, E.H.J.G., Verdijk, P., et al. 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 (2008), 1589–1597.
109. 109 Park, M.-H., Yang, D.-H., Kim, M.-H., et al. Alpha-type 1 polarized dendritic cells loaded with apoptotic allogeneic breast cancer cells can induce potent cytotoxic T lymphocytes against breast cancer. Cancer Res Treat 43 (2011), 56–66.
110. 110 Akiyama, Y., Oshita, C., Kume, A., et al. α-Type-1 polarized dendritic cell-based vaccination in recurrent high-grade glioma: a phase I clinical trial. BMC Cancer, 12, 2012, 623.
111. 111 Hansen, M., Hjortø, G.M., Donia, M., et al. Comparison of clinical grade type 1 polarized and standard matured dendritic cells for cancer immunotherapy. Vaccine 31 (2013), 639–646.
112. 112 Spadaro, F., Lapenta, C., Donati, S., et al. IFN-α enhances cross-presentation in human dendritic cells by modulating antigen survival, endocytic routing, and processing. Blood 119 (2012), 1407–1417.
113. 113 Shimizu, K., Fields, R.C., Giedlin, M., Mulé, J.J., Systemic administration of interleukin 2 enhances the therapeutic efficacy of dendritic cell-based tumor vaccines. Proc Natl Acad Sci U S A 96 (1999), 2268–2273 Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=26772&tool=pmcentrez&rendertype=abstract Accessed May 9, 2015.
114. 114 Redman, B.G., Chang, A.E., Whitfield, J., et al. Phase Ib trial assessing autologous, tumor-pulsed dendritic cells as a vaccine administered with or without IL-2 in patients with metastatic melanoma. J Immunother 31 (2008), 591–598.
115. 115 Martín-Fontecha, A., Lanzavecchia, A., Sallusto, F., Dendritic cell migration to peripheral lymph nodes. Handb Exp Pharmacol(188), 2009, 31–49.
116. 116 Simon, T., Fonteneau, J.-F., Grégoire, M., Dendritic cell preparation for immunotherapeutic interventions. Immunotherapy 1 (2009), 289–302.
117. 117 Fong, L., Brockstedt, D., Benike, C., Wu, L., Engleman, E.G., Dendritic cells injected via different routes induce immunity in cancer patients. J Immunol 166 (2001), 4254–4259 Available at: http://www.ncbi.nlm.nih.gov/pubmed/11238679 Accessed May 9, 2015.
118. 118 Verdijk, P., Aarntzen, E.H.J.G., Lesterhuis, W.J., et al. Limited amounts of dendritic cells migrate into the T-cell area of lymph nodes but have high immune activating potential in melanoma patients. Clin Cancer Res 15 (2009), 2531–2540.
119. 119 Yewdall, A.W., Drutman, S.B., Jinwala, F., Bahjat, K.S., Bhardwaj, N., CD8+ T cell priming by dendritic cell vaccines requires antigen transfer to endogenous antigen presenting cells. PLoS One, 5, 2010, e11144.
120. 120 Lesterhuis, W.J., de Vries, I.J.M., Schreibelt, G., et al. Route of administration modulates the induction of dendritic cell vaccine-induced antigen-specific T cells in advanced melanoma patients. Clin Cancer Res 17 (2011), 5725–5735.
121. 121 Endo, H., Saito, T., Kenjo, A., et al. Phase I trial of preoperative intratumoral injection of immature dendritic cells and OK-432 for resectable pancreatic cancer patients. J Hepatobiliary Pancreat Sci 19 (2012), 465–475.
122. 122 Guo, J., Zhu, J., Sheng, X., et al. Intratumoral injection of dendritic cells in combination with local hyperthermia induces systemic antitumor effect in patients with advanced melanoma. Int J Cancer 120 (2007), 2418–2425.
123. 123 Chi, K.-H., Liu, S.-J., Li, C.-P., et al. Combination of conformal radiotherapy and intratumoral injection of adoptive dendritic cell immunotherapy in refractory hepatoma. J Immunother 28 (2005), 129–135 Available at: http://www.ncbi.nlm.nih.gov/pubmed/15725956 Accessed May 9, 2015.
124. 124 Higham, E.M., Shen, C.-H., Wittrup, K.D., Chen, J., Cutting edge: delay and reversal of T cell tolerance by intratumoral injection of antigen-loaded dendritic cells in an autochthonous tumor model. J Immunol 184 (2010), 5954–5958.
125. 125 Small, E.J., Fratesi, P., Reese, D.M., et al. Immunotherapy of hormone-refractory prostate cancer with antigen-loaded dendritic cells. J Clin Oncol 18 (2000), 3894–3903 Available at: http://www.ncbi.nlm.nih.gov/pubmed/11099318 Accessed May 9, 2015.
126. 126 Aarntzen, E.H.J.G., Srinivas, M., Bonetto, F., et al. Targeting of 111In-labeled dendritic cell human vaccines improved by reducing number of cells. Clin Cancer Res 19 (2013), 1525–1533.
127. 127 Aarntzen, E.H., Srinivas, M., Schreibelt, G., et al. Reducing cell number improves the homing of dendritic cells to lymph nodes upon intradermal vaccination. Oncoimmunology, 2, 2013, e24661.
128. 128 Tacken, P.J., Figdor, C.G., Targeted antigen delivery and activation of dendritic cells in vivo: steps towards cost effective vaccines. Semin Immunol 23 (2011), 12–20.
129. 129 Caminschi, I., Maraskovsky, E., Heath, W.R., Targeting dendritic cells in vivo for cancer therapy. Front Immunol, 3, 2012, 13.
130. 130 Bonifaz, L., Bonnyay, D., Mahnke, K., Rivera, M., Nussenzweig, M.C., Steinman, R.M., Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance. J Exp Med 196 (2002), 1627–1638 Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2196060&tool=pmcentrez&rendertype=abstract Accessed May 6, 2015.
131. 131 Palucka, K., Banchereau, J., Dendritic-cell-based therapeutic cancer vaccines. Immunity 39 (2013), 38–48.
132. 132 Bonifaz, L.C., Bonnyay, D.P., Charalambous, A., et al. In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination. J Exp Med 199 (2004), 815–824.
133. 133 Leffers, N., Lambeck, A.J.A., Gooden, M.J.M., et al. Immunization with a P53 synthetic long peptide vaccine induces P53-specific immune responses in ovarian cancer patients, a phase II trial. Int J Cancer 125 (2009), 2104–2113.
134. 134 Walter, S., Weinschenk, T., Stenzl, A., et al. Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival. Nat Med 18 (2012), 1254–1261.
135. 135 Schuster, S.J., Neelapu, S.S., Gause, B.L., et al. Vaccination with patient-specific tumor-derived antigen in first remission improves disease-free survival in follicular lymphoma. J Clin Oncol 29 (2011), 2787–2794.
136. 136 Gupta, R., Emens, L.A., GM-CSF-secreting vaccines for solid tumors: moving forward. Discov Med 10 (2010), 52–60 Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3086372&tool=pmcentrez&rendertype=abstract Accessed June 29, 2015.
137. 137 Kusumoto, M., Umeda, S., Ikubo, A., et al. Phase 1 clinical trial of irradiated autologous melanoma cells adenovirally transduced with human GM-CSF gene. Cancer Immunol Immunother 50 (2001), 373–381 Available at: http://www.ncbi.nlm.nih.gov/pubmed/11676397 Accessed May 10, 2015.
138. 138 Higano, C.S., Corman, J.M., Smith, D.C., et al. Phase 1/2 dose-escalation study of a GM-CSF-secreting, allogeneic, cellular immunotherapy for metastatic hormone-refractory prostate cancer. Cancer 113 (2008), 975–984.
139. 139 Laheru, D., Lutz, E., Burke, J., et al. Allogeneic granulocyte macrophage colony-stimulating factor-secreting tumor immunotherapy alone or in sequence with cyclophosphamide for metastatic pancreatic cancer: a pilot study of safety, feasibility, and immune activation. Clin Cancer Res 14 (2008), 1455–1463.
140. 140 Filipazzi, P., Valenti, R., Huber, V., et al. Identification of a new subset of myeloid suppressor cells in peripheral blood of melanoma patients with modulation by a granulocyte-macrophage colony-stimulation factor-based antitumor vaccine. J Clin Oncol 25 (2007), 2546–2553.
141. 141 Ali, O.A., Huebsch, N., Cao, L., Dranoff, G., Mooney, D.J., Infection-mimicking materials to program dendritic cells in situ. Nat Mater 8 (2009), 151–158.
142. 142 Ali, O.A., Verbeke, C., Johnson, C., et al. Identification of immune factors regulating antitumor immunity using polymeric vaccines with multiple adjuvants. Cancer Res 74 (2014), 1670–1681.
143. 143 Liu, Y., Xiao, L., Joo, K.-I., Hu, B., Fang, J., Wang, P., In situ modulation of dendritic cells by injectable thermosensitive hydrogels for cancer vaccines in mice. Biomacromolecules 15 (2014), 3836–3845.
144. 144 Zitvogel, L., Regnault, A., Lozier, A., et al. Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes. Nat Med 4 (1998), 594–600 Available at: http://www.ncbi.nlm.nih.gov/pubmed/9585234 Accessed May 10, 2015.
145. 145 André, F., Chaput, N., Schartz, N.E.C., et al. Exosomes as potent cell-free peptide-based vaccine. I. Dendritic cell-derived exosomes transfer functional MHC class I/peptide complexes to dendritic cells. J Immunol 172 (2004), 2126–2136 Available at: http://www.ncbi.nlm.nih.gov/pubmed/14764678 Accessed March 20, 2015.
146. 146 Viaud, S., Terme, M., Flament, C., et al. Dendritic cell-derived exosomes promote natural killer cell activation and proliferation: a role for NKG2D ligands and IL-15Ralpha. PLoS One, 4, 2009, e4942.
147. 147 Näslund, T.I., Gehrmann, U., Qazi, K.R., Karlsson, M.C.I., Gabrielsson, S., Dendritic cell-derived exosomes need to activate both T and B cells to induce antitumor immunity. J Immunol 190 (2013), 2712–2719.
148. 148 Romagnoli, G.G., Zelante, B.B., Toniolo, P.A., Migliori, I.K., Barbuto, J.A.M., Dendritic cell-derived exosomes may be a tool for cancer immunotherapy by converting tumor cells into immunogenic targets. Front Immunol, 5, 2014, 692.
149. 149 Escudier, B., Dorval, T., Chaput, N., 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, 3, 2005, 10.
150. 150 Morse, M.A., Garst, J., Osada, T., et al. A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer. J Transl Med, 3, 2005, 9.
151. 151 Birkhäuser, F.D., Koya, R.C., Neufeld, C., et al. Dendritic cell–based immunotherapy in prevention and treatment of renal cell carcinoma. J Immunother 36 (2013), 102–111.
152. 152 Ahmed, M.S., Bae, Y.-S., Dendritic cell-based therapeutic cancer vaccines: past, present and future. Clin Exp Vaccine Res 3 (2014), 113–116.
153. 153 Sachamitr, P., Hackett, S., Fairchild, P.J., Induced pluripotent stem cells: challenges and opportunities for cancer immunotherapy. Front Immunol, 5, 2014, 176.
154. 154 Silk, K.M., Silk, J.D., Ichiryu, N., et al. Cross-presentation of tumour antigens by human induced pluripotent stem cell-derived CD141(+)XCR1+ dendritic cells. Gene Ther 19 (2012), 1035–1040.
155. 155 Topalian, S.L., Drake, C.G., Pardoll, D.M., Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell 27 (2015), 450–461.
156. 156 Gabrilovich, D.I., Chen, H.L., Girgis, K.R., et al. Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat Med 2 (1996), 1096–1103 Available at: http://www.ncbi.nlm.nih.gov/pubmed/8837607 Accessed June 30, 2015.
157. 157 Pickup, M., Novitskiy, S., Moses, H.L., The roles of TGFβ in the tumour microenvironment. Nat Rev Cancer 13 (2013), 788–799.
158. 158 Prendergast, G.C., Smith, C., Thomas, S., et al. Indoleamine 2,3-dioxygenase pathways of pathogenic inflammation and immune escape in cancer. Cancer Immunol Immunother 63 (2014), 721–735.
159. 159 Pardoll, D.M., The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12 (2012), 252–264.
160. 160 Sharma, P., Allison, J.P., The future of immune checkpoint therapy. Science 348 (2015), 56–61.
161. 161 Ridolfi, L., Petrini, M., Granato, A.M., et al. Low-dose temozolomide before dendritic-cell vaccination reduces (specifically) CD4+CD25++Foxp3+ regulatory T-cells in advanced melanoma patients. J Transl Med, 11, 2013, 135.
162. 162 Radojcic, V., Bezak, K.B., Skarica, M., et al. Cyclophosphamide resets dendritic cell homeostasis and enhances antitumor immunity through effects that extend beyond regulatory T cell elimination. Cancer Immunol Immunother 59 (2010), 137–148.
163. 163 Dannull, J., Su, Z., Rizzieri, D., et al. Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J Clin Invest 115 (2005), 3623–3633.
164. 164 Morse, M.A., Hobeika, A.C., Osada, T., et al. Depletion of human regulatory T cells specifically enhances antigen-specific immune responses to cancer vaccines. Blood 112 (2008), 610–618.
165. 165 Baur, A.S., Lutz, M.B., Schierer, S., et al. Denileukin diftitox (ONTAK) induces a tolerogenic phenotype in dendritic cells and stimulates survival of resting Treg. Blood 122 (2013), 2185–2194.
166. 166 Ribas, A., Comin-Anduix, B., Chmielowski, B., et al. Dendritic cell vaccination combined with CTLA4 blockade in patients with metastatic melanoma. Clin Cancer Res 15 (2009), 6267–6276.
167. 167 Wolchok, J.D., Hoos, A., O'Day, S., et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res 15 (2009), 7412–7420.