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The ABCs of artificial antigen presentation

Abstract

Artificial antigen presentation aims to accelerate the establishment of therapeutic cellular immunity. Artificial antigen-presenting cells (AAPCs) and their cell-free substitutes are designed to stimulate the expansion and acquisition of optimal therapeutic features of T cells before therapeutic infusion, without the need for autologous antigen-presenting cells. Compelling recent advances include fibroblast AAPCs that process antigens, magnetic beads that are antigen specific, novel T-cell costimulatory combinations, the augmentation of therapeutic potency of adoptively transferred T lymphocytes by interleukin-15, and the safe use of dendritic cell-derived exosomes pulsed with tumor antigen. Whereas the safety and potency of the various systems warrant further preclinical and clinical studies, these emerging technologies are poised to have a major impact on adoptive T-cell therapy and the investigation of T cell–mediated immunity.

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Figure 2: Representation of the T cell–APC interaction.

Bob Crimi

Figure 1: Examples of artificial antigen presentation.

Bob Crimi

References

  1. 1

    Riddell, S.R., Murata, M., Bryant, S. & Warren, E.H. T-cell therapy of leukemia. Cancer Control 9, 114–122 (2002).

    PubMed  Google Scholar 

  2. 2

    Papadopoulos, E.B. et al. Infusions of donor leukocytes to treat Epstein-Barr virus-associated lymphoproliferative disorders after allogeneic bone marrow transplantation. N. Engl. J. Med. 330, 1185–1191 (1994).

    CAS  PubMed  Google Scholar 

  3. 3

    Savoldo, B., Heslop, H.E. & Rooney, C.M. The use of cytotoxic T cells for the prevention and treatment of Epstein-Barr virus induced lymphoma in transplant recipients. Leukemia Lymphoma 39, 455–464 (2000).

    CAS  PubMed  Google Scholar 

  4. 4

    Yee, C. et al. Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastatic melanoma: in vivo persistence, migration, and antitumor effect of transferred T cells. Proc. Natl. Acad. Sci. USA 99, 16168–16173 (2002).

    CAS  Google Scholar 

  5. 5

    Dudley, M.E. et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 298, 850–854 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. 6

    Hori, S., Takahashi, T. & Sakaguchi, S. Control of autoimmunity by naturally arising regulatory CD4+ T cells. Adv. Immunol. 81, 331–371 (2003).

    CAS  PubMed  Google Scholar 

  7. 7

    Karim, M., Kingsley, C.I., Bushell, A.R., Sawitzki, B.S. & Wood, K.J. Alloantigen-induced CD25+CD4+ regulatory T cells can develop in vivo from CD25CD4+precursors in a thymus-independent process. J. Immunol. 172, 923–928 (2004).

    CAS  Google Scholar 

  8. 8

    Janeway, C.A. Jr., Walport, M. & Shlomchik, M.J. Immunobiology, edn. 5 (Garland Publishing, New York, 2001).

    Google Scholar 

  9. 9

    Janetzki, S., Song, P., Gupta, V., Lewis, J.J. & Houghton, A.N. Insect cells as HLA-restricted antigen-presenting cells for the IFN-gamma elispot assay. J. Immunol. Methods 234, 1–12 (2000).

    CAS  PubMed  Google Scholar 

  10. 10

    Cai, Z. et al. Transfected Drosophila cells as a probe for defining the minimal requirements for stimulating unprimed CD8+ T cells. Proc. Natl. Acad. Sci. USA 93, 14736–14741 (1996).

    CAS  PubMed  Google Scholar 

  11. 11

    Jackson, M.R., Song, E.S., Yang, Y. & Peterson, P.A. Empty and peptide-containing conformers of class I major histocompatibility complex molecules expressed in Drosophila melanogaster cells. Proc. Natl. Acad. Sci. USA 89, 12117–12121 (1992).

    CAS  PubMed  Google Scholar 

  12. 12

    Sun, S. et al. Dual function of Drosophila cells as APCs for naive CD8+ T cells: implications for tumor immunotherapy. Immunity 4, 555–564 (1996).

    CAS  PubMed  Google Scholar 

  13. 13

    Schoenberger, S.P. et al. Efficient direct priming of tumor-specific cytotoxic T lymphocyte in vivo by an engineered APC. Cancer Res. 58, 3094–3100 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 14

    Latouche, J.B. & Sadelain, M. Induction of human cytotoxic T lymphocytes by artificial antigen-presenting cells. Nat. Biotechnol. 18, 405–409 (2000).

    CAS  PubMed  Google Scholar 

  15. 15

    Papanicolaou, G.A. et al. Rapid expansion of cytomegalovirus-specific cytotoxic T lymphocytes by artificial antigen-presenting cells expressing a single HLA allele. Blood 102, 2498–2505 (2003).

    CAS  PubMed  Google Scholar 

  16. 16

    Maus, M.V. et al. Ex vivo expansion of polyclonal and antigen-specific cytotoxic T lymphocytes by artificial APCs expressing ligands for the T-cell receptor, CD28 and 4-1BB. Nat. Biotechnol. 20, 143–148 (2002).

    CAS  PubMed  Google Scholar 

  17. 17

    Thomas, A.K., Maus, M.V., Shalaby, W.S., June, C.H. & Riley, J.L. A cell-based artificial antigen-presenting cell coated with anti-CD3 and CD28 antibodies enables rapid expansion and long-term growth of CD4 T lymphocytes. Clin. Immunol. 105, 259–272 (2002).

    CAS  PubMed  Google Scholar 

  18. 18

    Levine, B.L. et al. Effects of CD28 costimulation on long-term proliferation of CD4+ T cells in the absence of exogenous feeder cells. J. Immunol. 159, 5921–5930 (1997).

    CAS  PubMed  Google Scholar 

  19. 19

    Levine, B.L. et al. Large-scale production of CD4+ T cells from HIV-1-infected donors after CD3/CD28 costimulation. J. Hematother. 7, 437–448 (1998).

    CAS  PubMed  Google Scholar 

  20. 20

    Levine, B.L. et al. Adoptive transfer of costimulated CD4+ T cells induces expansion of peripheral T cells and decreased CCR5 expression in HIV infection. Nat. Med. 8, 47–53 (2002).

    CAS  PubMed  Google Scholar 

  21. 21

    Laux, I. et al. Response differences between human CD4(+) and CD8(+) T-cells during CD28 costimulation: implications for immune cell-based therapies and studies related to the expansion of double-positive T-cells during aging. Clin. Immunol. 96, 187–197 (2000).

    CAS  PubMed  Google Scholar 

  22. 22

    Oelke, M. et al. Ex vivo induction and expansion of antigen-specific cytotoxic T cells by HLA-Ig-coated artificial antigen-presenting cells. Nat. Med. 9, 619–624 (2003).

    CAS  PubMed  Google Scholar 

  23. 23

    Maus, M.V., Riley, J.L., Kwok, W.W., Nepom, G.T. & June, C.H. HLA tetramer-based artificial antigen-presenting cells for stimulation of CD4+ T cells. Clin. Immunol. 106, 16–22 (2003).

    CAS  PubMed  Google Scholar 

  24. 24

    Prakken, B. et al. Artificial antigen-presenting cells as a tool to exploit the immune 'synapse' Nat. Med. 6, 1406–1410 (2000).

    CAS  PubMed  Google Scholar 

  25. 25

    Zitvogel, L. et al. Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes. Nat. Med. 4, 594–600 (1998).

    CAS  PubMed  Google Scholar 

  26. 26

    Wolfers, J. et al. Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat. Med. 7, 297–303 (2001).

    CAS  PubMed  Google Scholar 

  27. 27

    Thery, C., Zitvogel, L. & Amigorena, S. Exosomes: composition, biogenesis and function. Nat. Rev. Immunol. 2, 569–579 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28

    Andre, F. et al. Malignant effusions and immunogenic tumour-derived exosomes. Lancet 360, 295–305 (2002).

    CAS  PubMed  Google Scholar 

  29. 29

    Chaput, N. et al. Exosomes as potent cell-free peptide-based vaccine. II. Exosomes in CpG adjuvants efficiently prime naive Tc1 lymphocytes leading to tumor rejection. J. Immunol. 172, 2137–2146 (2004).

    CAS  PubMed  Google Scholar 

  30. 30

    Chaput, N., Schartz, N.E., Andre, F. & Zitvogel, L. Exosomes for immunotherapy of cancer. Adv. Exp. Med. Biol. 532, 215–221 (2003).

    CAS  PubMed  Google Scholar 

  31. 31

    Raposo, G. et al. B lymphocytes secrete antigen-presenting vesicles. J. Exp. Med. 183, 1161–1172 (1996).

    CAS  PubMed  Google Scholar 

  32. 32

    Hsu, D.H. et al. Exosomes as a tumor vaccine: enhancing potency through direct loading of antigenic peptides. J. Immunother. 26, 440–450 (2003).

    CAS  PubMed  Google Scholar 

  33. 33

    Banchereau, J. & Steinman, R.M. Dendritic cells and the control of immunity. Nature 392, 245–252 (1998).

    CAS  Google Scholar 

  34. 34

    Pardoll, D.M. Spinning molecular immunology into successful immunotherapy. Nat. Rev. Immunol. 2, 227–238 (2002).

    CAS  PubMed  Google Scholar 

  35. 35

    Stoll, S., Delon, J., Brotz, T.M. & Germain, R.N. Dynamic imaging of T cell-dendritic cell interactions in lymph nodes. Science 296, 1873–1876 (2002).

    Google Scholar 

  36. 36

    Jung, S. et al. In vivo depletion of CD11c(+) dendritic cells abrogates priming of CD8(+) T cells by exogenous cell-associated antigens. Immunity 17, 211–220 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. 37

    Riddell, S.R. & Greenberg, P.D. T-cell therapy of cytomegalovirus and human immunodeficiency virus infection. J. Antimicrob. Chemother. 45 Suppl T3, 35–43 (2000).

    CAS  PubMed  Google Scholar 

  38. 38

    Bender, A., Sapp, M., Schuler, G., Steinman, R.M. & Bhardwaj, N. Improved methods for the generation of dendritic cells from nonproliferating progenitors in human blood. J. Immunol. Methods 196, 121–135 (1996).

    CAS  Google Scholar 

  39. 39

    Reddy, A., Sapp, M., Feldman, M., Subklewe, M. & Bhardwaj, N. A monocyte conditioned medium is more effective than defined cytokines in mediating the terminal maturation of human dendritic cells. Blood 90, 3640–3646 (1997).

    CAS  PubMed  Google Scholar 

  40. 40

    Mitchell, M.S. et al. Phase I trial of adoptive immunotherapy with cytolytic T lymphocytes immunized against a tyrosinase epitope. J. Clin. Oncol. 20, 1075–1086 (2002).

    CAS  PubMed  Google Scholar 

  41. 41

    Krause, A. et al. Antigen-dependent CD28 signaling selectively enhances survival and proliferation in genetically modified activated human primary T lymphocytes. J. Exp. Med. 188, 619–626 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. 42

    Gong, M.C. et al. Cancer patient T cells genetically targeted to prostate-specific membrane antigen specifically lyse prostate cancer cells and release cytokines in response to prostate-specific membrane antigen. Neoplasia 1, 123–127 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. 43

    Johnson, D.R. Differential expression of human major histocompatibility class I loci: HLA-A, -B, and -C. Hum. Immunol. 61, 389–396 (2000).

    CAS  PubMed  Google Scholar 

  44. 44

    Delbrück, A. in Structural Chemistry and Molecular Biology. (eds. Davidson, N. & Rich, A.) 198–215 (Freeman, San Francisco, 1968).

    Google Scholar 

  45. 45

    Kim, J., Mosior, M., Chung, L.A., Wu, H. & McLaughlin, S. Binding of peptides with basic residues to membranes containing acidic phospholipids. Biophys. J. 60, 135–148 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. 46

    Kim, J., Shishido, T., Jiang, X., Aderem, A. & McLaughlin, S. Phosphorylation, high ionic strength, and calmodulin reverse the binding of MARCKS to phospholipid vesicles. J. Biol. Chem. 269, 28214–28219 (1994).

    CAS  PubMed  Google Scholar 

  47. 47

    McLaughlin, S., Wang, J., Gambhir, A. & Murray, D. PIP(2) and proteins: interactions, organization, and information flow. Annu. Rev. Biophys. Biomol. Struct. 31, 151–175 (2002).

    CAS  Google Scholar 

  48. 48

    Mosior, M. & McLaughlin, S. Electrostatics and reduction of dimensionality produce apparent cooperativity when basic peptides bind to acidic lipids in membranes. Biochim. Biophys. Acta. 1105, 185–187 (1992).

    CAS  PubMed  Google Scholar 

  49. 49

    Lee, S.J., Hori, Y., Groves, J.T., Dustin, M.L. & Chakraborty, A.K. The synapse assembly model. Trends Immunol. 23, 500–502 (2002).

    CAS  PubMed  Google Scholar 

  50. 50

    Lee, S.J., Hori, Y., Groves, J.T., Dustin, M.L. & Chakraborty, A.K. Correlation of a dynamic model for immunological synapse formation with effector functions: two pathways to synapse formation. Trends Immunol. 23, 492–499 (2002).

    CAS  PubMed  Google Scholar 

  51. 51

    Hwang, I., Shen, X. & Sprent, J. Direct stimulation of naive T cells by membrane vesicles from antigen-presenting cells: distinct roles for CD54 and B7 molecules. Proc. Natl. Acad. Sci. USA 100, 6670–6675 (2003).

    CAS  PubMed  Google Scholar 

  52. 52

    Gett, A.V., Sallusto, F., Lanzavecchia, A. & Geginat, J. T cell fitness determined by signal strength. Nat. Immunol. 4, 355–360 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. 53

    Sadelain, M., Riviere, I. & Brentjens, R. Targeting tumours with genetically enhanced T lymphocytes. Nat. Rev. Cancer 3, 35–45 (2003).

    CAS  PubMed  Google Scholar 

  54. 54

    Lohr, J., Knoechel, B., Jiang, S., Sharpe, A.H. & Abbas, A.K. The inhibitory function of B7 costimulators in T cell responses to foreign and self-antigens. Nat. Immunol. 4, 664–669 (2003).

    CAS  PubMed  Google Scholar 

  55. 55

    Topp, M.S. et al. Restoration of CD28 expression in CD28+-CD8+ memory effector T cells reconstitutes antigen-induced IL-2 production. J. Exp. Med. 198, 947–955 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. 56

    Wen, T., Bukczynski, J. & Watts, T.H. 4-1BB ligand-mediated costimulation of human T cells induces CD4 and CD8 T cell expansion, cytokine production, and the development of cytolytic effector function. J. Immunol. 168, 4897–4906 (2002).

    CAS  PubMed  Google Scholar 

  57. 57

    Melero, I. et al. Amplification of tumor immunity by gene transfer of the co-stimulatory 4-1BB ligand: synergy with the CD28 co-stimulatory pathway. Eur. J. Immunol. 28, 1116–1121 (1998).

    CAS  PubMed  Google Scholar 

  58. 58

    Rogers, P.R., Song, J., Gramaglia, I., Killeen, N. & Croft, M. OX40 promotes Bcl-xL and Bcl-2 expression and is essential for long-term survival of CD4 T cells. Immunity 15, 445–455 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. 59

    Kikuchi, T., Moore, M.A. & Crystal, R.G. Dendritic cells modified to express CD40 ligand elicit therapeutic immunity against preexisting murine tumors. Blood 96, 91–99 (2000).

    CAS  PubMed  Google Scholar 

  60. 60

    Kikuchi, T., Worgall, S., Singh, R., Moore, M.A. & Crystal, R.G. Dendritic cells genetically modified to express CD40 ligand and pulsed with antigen can initiate antigen-specific humoral immunity independent of CD4+ T cells. Nat. Med. 6, 1154–1159 (2000).

    CAS  PubMed  Google Scholar 

  61. 61

    Overwijk, W.W. et al. Tumor regression and autoimmunity after reversal of a functionally tolerant state of self-reactive CD8+ T cells. J. Exp. Med. 198, 569–580 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. 62

    Rottman, J.B. et al. The costimulatory molecule ICOS plays an important role in the immunopathogenesis of EAE. Nat. Immunol. 2, 605–611 (2001).

    CAS  PubMed  Google Scholar 

  63. 63

    Salama, A.D. et al. Interaction between ICOS-B7RP1 and B7-CD28 costimulatory pathways in alloimmune responses in vivo. Am. J. Transplant. 3, 390–395 (2003).

    CAS  PubMed  Google Scholar 

  64. 64

    Sporici, R.A. & Perrin, P.J. Costimulation of memory T-cells by ICOS: a potential therapeutic target for autoimmunity? Clin. Immunol. 100, 263–269 (2001).

    CAS  PubMed  Google Scholar 

  65. 65

    Villegas, E.N. et al. A role for inducible costimulator protein in the CD28- independent mechanism of resistance to Toxoplasma gondii. J. Immunol. 169, 937–943 (2002).

    CAS  PubMed  Google Scholar 

  66. 66

    Yoshinaga, S.K. et al. T-cell co-stimulation through B7RP-1 and ICOS. Nature 402, 827–832 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. 67

    Rosenberg, S.A. et al. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. N. Engl. J. Med. 319, 1676–1680 (1988).

    CAS  PubMed  Google Scholar 

  68. 68

    Bhardwaj, N., Seder, R.A., Reddy, A. & Feldman, M.V. IL-12 in conjunction with dendritic cells enhances antiviral CD8+ CTL responses in vitro. J. Clin. Invest. 98, 715–722 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. 69

    Gajewski, T.F. Integrating IL-12 into therapeutic cancer vaccines. Cancer Chemother. Biol. Response Modif. 20, 343–349 (2002).

    CAS  PubMed  Google Scholar 

  70. 70

    Portielje, J.E., Gratama, J.W., van Ojik, H.H., Stoter, G. & Kruit, W.H. IL-12: a promising adjuvant for cancer vaccination. Cancer Immunol. Immunother. 52, 133–144 (2003).

    CAS  PubMed  Google Scholar 

  71. 71

    Puccetti, P., Belladonna, M.L. & Grohmann, U. Effects of IL-12 and IL-23 on antigen-presenting cells at the interface between innate and adaptive immunity. Crit. Rev. Immunol. 22, 373–390 (2002).

    CAS  PubMed  Google Scholar 

  72. 72

    Schluns, K.S. & Lefrancois, L. Cytokine control of memory T-cell development and survival. Nat. Rev. Immunol. 3, 269–279 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. 73

    Fehniger, T.A., Cooper, M.A. & Caligiuri, M.A. Interleukin-2 and interleukin-15: immunotherapy for cancer. Cytokine Growth Factor Rev. 13, 169–183 (2002).

    CAS  PubMed  Google Scholar 

  74. 74

    Waldmann, T. The contrasting roles of IL-2 and IL-15 in the life and death of lymphocytes: implications for the immunotherapy of rheumatological diseases. Arthritis Res. 4 Suppl 3, S161–S167 (2002).

    PubMed  PubMed Central  Google Scholar 

  75. 75

    Waldmann, T.A., Dubois, S. & Tagaya, Y. Contrasting roles of IL–2 and IL-15 in the life and death of lymphocytes: implications for immunotherapy. Immunity 14, 105–110 (2001).

    CAS  PubMed  Google Scholar 

  76. 76

    Alpdogan, O. et al. IL-7 enhances peripheral T cell reconstitution after allogeneic hematopoietic stem cell transplantation. J. Clin. Invest. 112, 1095–1107 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. 77

    Kaech, S.M. et al. Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells. Nat. Immunol. 4, 1191–1198 (2003).

    CAS  Google Scholar 

  78. 78

    Nugeyre, M.T. et al. IL-7 stimulates T cell renewal without increasing viral replication in simian immunodeficiency virus-infected macaques. J. Immunol. 171, 4447–4453 (2003).

    CAS  PubMed  Google Scholar 

  79. 79

    Strengell, M., Sareneva, T., Foster, D., Julkunen, I. & Matikainen, S. IL-21 up-regulates the expression of genes associated with innate immunity and Th1 response. J. Immunol. 169, 3600–3605 (2002).

    PubMed  Google Scholar 

  80. 80

    Wong, P. & Pamer, E.G. Cutting edge: antigen-independent CD8 T cell proliferation. J. Immunol. 166, 5864–5868 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. 81

    Brentjens, R.J. et al. Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15. Nat. Med. 9, 279–286 (2003).

    CAS  PubMed  Google Scholar 

  82. 82

    Shand, A. & Forbes, A. Potential therapeutic role for cytokine or adhesion molecule manipulation in Crohn's disease: in the shadow of infliximab? Int. J. Colorectal. Dis. 18, 1–11 (2003).

    PubMed  Google Scholar 

  83. 83

    Parrish-Novak, J., Foster, D.C., Holly, R.D. & Clegg, C.H. Interleukin-21 and the IL-21 receptor: novel effectors of NK and T cell responses. J. Leukoc. Biol. 72, 856–863 (2002).

    CAS  PubMed  Google Scholar 

  84. 84

    Wurster, A.L. et al. Interleukin 21 is a T helper (Th) cell 2 cytokine that specifically inhibits the differentiation of naive Th cells into interferon gamma-producing Th1 cells. J. Exp. Med. 196, 969–977 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. 85

    Andre, F. et al. Tumor-derived exosomes: a new source of tumor rejection antigens. Vaccine 20 Suppl 4, A28–A31 (2002).

    CAS  PubMed  Google Scholar 

  86. 86

    Chaput, N. et al. Exosomes and anti-tumour immunotherapy. Bull. Cancer 90, 695–698 (2003).

    PubMed  Google Scholar 

  87. 87

    Wang, H.Y. et al. Tumor-specific human CD4+ regulatory T cells and their ligands: implications for immunotherapy. Immunity 20, 107–118 (2004).

    CAS  PubMed  Google Scholar 

  88. 88

    Laport, G.G. et al. Adoptive transfer of costimulated T cells induces lymphocytosis in patients with relapsed/refractory non-Hodgkin lymphoma following CD34+-selected hematopoietic cell transplantation. Blood 102, 2004–2013 (2003).

    CAS  PubMed  Google Scholar 

  89. 89

    Rapoport, A.P. et al. Molecular remission of CML after autotransplantation followed by adoptive transfer of costimulated autologous T cells. Bone Marrow Transplant. 33, 53–60 (2004).

    CAS  PubMed  Google Scholar 

  90. 90

    Andre, F. 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, 2126–2136 (2004).

    CAS  PubMed  Google Scholar 

  91. 91

    Hurwitz, A.A., Yanover, P., Markowitz, M., Allison, J.P. & Kwon, E.D. Prostate cancer: advances in immunotherapy. BioDrugs 17, 131–138 (2003).

    CAS  PubMed  Google Scholar 

  92. 92

    Hurwitz, A.A., Yu, T.F., Leach, D.R. & Allison, J.P. CTLA-4 blockade synergizes with tumor-derived granulocyte-macrophage colony-stimulating factor for treatment of an experimental mammary carcinoma. Proc. Natl. Acad. Sci. USA 95, 10067–10071 (1998).

    CAS  Google Scholar 

  93. 93

    Phan, G.Q. et al. Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc. Natl. Acad. Sci. USA 100, 8372–8377 (2003).

    CAS  PubMed  Google Scholar 

  94. 94

    van Elsas, A., Hurwitz, A.A. & Allison, J.P. Combination immunotherapy of B16 melanoma using anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation. J. Exp. Med. 190 355–366 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. 95

    Seder, R.A. & Ahmed, R. Similarities and differences in CD4+ and CD8+ effector and memory T cell generation. Nat. Immunol. 4, 835–842 (2003).

    CAS  Google Scholar 

  96. 96

    Ahn, H.J. et al. A mechanism underlying synergy between IL-12 and IFN-gamma-inducing factor in enhanced production of IFN-gamma. J. Immunol. 159, 2125–2131 (1997).

    CAS  PubMed  Google Scholar 

  97. 97

    Robinson, D. et al. IGIF does not drive Th1 development but synergizes with IL-12 for interferon-gamma production and activates IRAK and NFkappaB. Immunity 7, 571–581 (1997).

    CAS  Google Scholar 

  98. 98

    Tatsumi, T. et al. Intratumoral delivery of dendritic cells engineered to secrete both interleukin (IL)-12 and IL-18 effectively treats local and distant disease in association with broadly reactive Tc1-type immunity. Cancer Res. 63, 6378–6386 (2003).

    CAS  PubMed  Google Scholar 

  99. 99

    Watford, W.T., Moriguchi, M., Morinobu, A. & O'Shea, J.J. The biology of IL-12: coordinating innate and adaptive immune responses. Cytokine Growth Factor Rev. 14, 361–368 (2003).

    CAS  PubMed  Google Scholar 

  100. 100

    Bromley, S.K. et al. The immunological synapse. Annu. Rev. Immunol. 19, 375–396 (2001).

    CAS  Google Scholar 

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Acknowledgements

Our work is supported by National Institutes of Health grants CA-59350, CA-08748 and CA-09512 to J.V.K., I.R. and M.S.

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Kim, J., Latouche, JB., Rivière, I. et al. The ABCs of artificial antigen presentation. Nat Biotechnol 22, 403–410 (2004). https://doi.org/10.1038/nbt955

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