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Unleashing the Therapeutic Potential of Dendritic and T Cell Therapies Using RNA Interference

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RNA Interference and CRISPR Technologies

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2115))

Abstract

Therapeutic dendritic cell (DC) cancer vaccines work to boost the body’s immune system to fight a cancer. Although this type of immunotherapy often leads to the activation of tumor-specfic T cells, clinical responses are fairly low, arguing for the need to improve the design of DC-based vaccines. Recent studies revealed a promising strategy of combining DC vaccines with small interfering RNAs (siRNAs) targeting immunosuppressive signals such as checkpoint receptors. Similarly, incorporating checkpoint siRNA blockers in adoptive T-cell therapy to amplify cytotoxic T lymphocyte responses is now being tested in the clinic. The development of the next generation of cancer immunotherapies using siRNA technology will hopefuly benefit patients with various cancer types including those who did not respond to current therapies. This review highlights the latest advances in RNA interference technology to improve the therapeutic efficacy of DC cancer vaccines and T cell therapy.

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References

  1. Liu K, Nussenzweig MC (2010) Origin and development of dendritic cells. Immunol Rev 234:45–54

    Article  CAS  PubMed  Google Scholar 

  2. Palucka K, Banchereau J, Mellman I (2010) Designing vaccines based on biology of human dendritic cell subsets. Immunity 33:464–478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Chen L (2004) Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity. Nat Rev Immunol 4:336–347

    Article  CAS  PubMed  Google Scholar 

  4. Schwartz RH (1992) Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. Cell 71:1065–1068

    Article  CAS  PubMed  Google Scholar 

  5. Fife BT, Pauken KE, Eagar TN, Obu T, Wu J, Tang Q, Azuma M, Krummel MF, Bluestone JA (2009) Interaction between PD-1 and PD-L-1 promote tolerance by blocking the TcR-induced stop signal. Nat Immunol 10:1185–1192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Chung CY, Ysebaert D, Berneman ZN, Cools N (2013) Dendritic cells: cellular mediators for immunological tolerance. Clin Dev Immunol 2013:972865

    Google Scholar 

  7. Munn DH, Mellor AL (2007) Indolamine 2,3-dioxygenase and tumor-induced tolerance. J Clin Invest 17:1147–1154

    Article  CAS  Google Scholar 

  8. Corinti S, Albanesis C, la Salsa A, Pastore S, Girolomoni G (2001) Regulatory activity of autocrine IL-10 on dendritic cell functions. J Immunol 166:4312–4320

    Article  CAS  PubMed  Google Scholar 

  9. Yu CI, Becker C, Wang Y, Marches F, Helft J, Leboeuf M, Anguiano E, Pourpe S, Goller K, Pascual V, Banchereau J, Merad M, Palucka K (2013) Human CD1c+ dendritic cells drive the differentiation of CD103+ CD8+ mucosal effector T cells via the cytokine TGF-β. Immunity 38:818–830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Mahnke K, Johnson TS, Ring A, Enk AH (2007) Tolerogenic dendritic cells and regulatory T cells: a two-way relationship. J Dermatol 46:159–167

    CAS  Google Scholar 

  11. Zhao H, Liao X, Kang Y (2017) Tregs: where we are and what comes next? Front Immunol 8:1578. eCollection 2017

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Zheng P, Zhou Z (2015) Human cancer immunotherapy with PD-1/PD-L1 blockade. Biomark Cancer 7(Suppl 2):15–18. eCollection

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Anguille S, Smits EL, Lion E, van Tendeloo VF, Berneman ZN (2014) Clinical use of dendritic cells for cancer therapy. Lancet Ocol 15:e257–e267

    Article  CAS  Google Scholar 

  14. Palucka K, Banchereau J (2013) Human dendritic cell subsets in vaccination. Curr Opin Immunol 25:396–402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Flatekval GF, Sioud M (2009) Modulation of dendritic cell maturation and function with mono- and bifunctional small interfering RNAs targeting indoleamine 2,3-dioxygenase. Immunology 128:e837–e848

    Article  PubMed  PubMed Central  Google Scholar 

  16. Steinman RM, Hawiger D, Nussenzweig MC (2003) Tolerogenic dendritic cells. Annu Rev Immunol 21:685–711

    Article  CAS  PubMed  Google Scholar 

  17. Beatty GL, Gladney WL (2015) Immune escape mechanisms as a guide for cancer immunotherapy. Clin Cancer Res 15:687–692

    Article  CAS  Google Scholar 

  18. Munn DH, Mellor AL (2004) IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat Rev Immunol 4:762–774

    Article  PubMed  CAS  Google Scholar 

  19. Munn DH, Sharma MD, Hou D, Baban B, Lee JR, Antonia SJ et al (2004) Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in draining-draining lymph nodes. J Clin Invest 114:280–290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Fallarino F, Grohmann U, Vacca C et al (2002) T cell apoptosis by tryptophan catabolism. Cell Death Differ 9:1069–1077

    Article  CAS  PubMed  Google Scholar 

  21. Terness P, Bauer TM, Röse L, Dufter C, Watzlik A, Simon H, Opelz G (2002) Inhibition of allogeneic T cell proliferation by indoleamine 2,3-dioxygenase-expressing dendritic cells: mediation of suppression by tryptophan metabolites. J Exp Med 96:447–457

    Article  CAS  Google Scholar 

  22. Liu H, Liu L, Liu K, Bizargity P, Hancock WW, Visner GA (2009) Reduced cytotoxic function of effector CD8+ T cells is responsible for indoleamine 2,3-dioxygenase-dependent immune suppression. J Immunol 183:1022–1031

    Article  CAS  PubMed  Google Scholar 

  23. Platten M, Wick W, Van den Eynde BJ (2012) Tryptophan catabolism in cancer: beyond IDO and tryptophan depletion. Cancer Res 72:5435–5440

    Article  CAS  PubMed  Google Scholar 

  24. Grohmann U, Orabona C, Fallarino F, Vacca C, Calcinaro F, Falorni A, Candeloro P, Belladonna ML, Bianchi R, Fioretti MC, Puccetti P (2002) CTLA-4-Ig regulates tryptophan catabolism in vivo. Nat Immunol 3:1097–1101

    Article  CAS  PubMed  Google Scholar 

  25. Wobster M, Voigt H, Houben R, Eggert AO, Freiwald M, Kaemmerer U et al (2007) Dendritic cell based antitumor vaccination: impact of functional indoleamine 2,3-dioxygenase expression. Cancer Immunol Immunother 56:1017–1024

    Article  CAS  Google Scholar 

  26. Furset G, Fløisand Y, Sioud M (2007) Impaired expression of indoleamine 2, 3-dioxygenase in monocyte-derived dendritic cells in response to Toll-like receptor-7/8 ligands. Immunology 123:263–271

    PubMed  Google Scholar 

  27. Flatekval GF (2019) Insights into siRNA-sensing by the immune system and immunotherapeutic strategies using siRNA. PhD thesis, University of Oslo, December 2019.

    Google Scholar 

  28. Zheng X, Koropatnick J, Chen D et al (2013) Silencing IDO in dendritic cells: a novel approach to enhance cancer immunotherapy in a murine breast cancer model. Int J Cancer 132:967–977

    Article  CAS  PubMed  Google Scholar 

  29. Sæbø-Larsen S, Fossberg E, Gaudernack G (2002) mRNA-based electrotransfection of human dendritic cells and induction of cytotoxic T lymphocyte responses against the telomerase catalytic subunit (hTERT). J Immunol Methods 259:191–203

    Article  Google Scholar 

  30. Sioud M, Saebøe-Larssen S, Hetland TE, Kaern J, Mobergslien A, Kvalheim G (2013) Silencing of indoleamine 2,3-dioxygenase in dendritic cell cancer vaccines: evaluation in vitro and in cancer patients. Int J Oncol 43:280–288

    Article  CAS  PubMed  Google Scholar 

  31. Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL, Shay JW (1994) Specific association of human telomerase activity with immortal cells and cancer. Science 266:2011–2015

    Article  CAS  PubMed  Google Scholar 

  32. Marian CO, Cho SK, McEllin BM, Maher EA, Hatanpaa KJ, Madden CJ, Mickey BE, Wright WE, Shay JW, Bachoo RM (2010) The telomerase antagonist, imetelstat, efficiently targets glioblastoma tumor-initiating cells leading to decreased proliferation and tumor growth. Clin Cancer Res 16:154–163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Sharma P, Allison JP (2015) The future of immune checkpoint therapy. Science 348:56–61

    Article  CAS  PubMed  Google Scholar 

  34. Sioud M, Nyakas M, Sæbøe-Larssen S, Mobergslien A, Aamdal S, Kvalheim G (2016) Diversification of antitumour immunity in a patient with metastatic melanoma treated with ipilimumab and an IDO-silenced dendritic cell vaccine. Case Rep Med 2016:9639585

    Article  PubMed  PubMed Central  Google Scholar 

  35. Francisco LM, Sage PT, Sharpe AH (2010) The PD-1 pathway in tolerance and autoimmunity. Immunol Rev 236:219–242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Schadendorf D, Hodi FS et al (2015) Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma. J Clin Oncol 33:1889–1894

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Ohaegbulam KC, Assal A, Lazar-Molnar E, Yao Y, Zang X (2015) Human cancer immunotherapy with antibodies to the PD-1 and PD-L1 pathway. Trends Mol Med 21:24–33

    Article  CAS  PubMed  Google Scholar 

  38. Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A et al (2014) Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med 371:2189–2199

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ et al (2015) Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockage in non-small cell lung cancer. Science 348:124–128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Boussiotis VA (2014) Somatic mutations and immunotherapy outcome with CTLA-4 blockade in melanoma. N Engl J Med 371:2230–2232

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Hobo W, Novobrantseva TI, Fredrix H, Wong J, Milstein S, Epstein-Barash H et al (2013) Improving dendritic cell vaccine immunogenicity by silencing PD-1 ligands using siRNA-lipid nanoparticles combined with antigen mRNA electroporation. Cancer Immunol Immunother 62:285–297

    Article  CAS  PubMed  Google Scholar 

  42. Wang S, Wang Y, Liu J, Shao S, Li X, Gao J et al (2014) Silencing B7-H1 enhances the anti-tumor effect of bladder cancer antigen-loaded dendritic cell vaccine in vitro. Onco Targets Ther 7:1389–1396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Hobo W, Mams F, Adistry N, de Witte T, Schaap N, van der Voort R et al (2010) siRNA silencing of PD-L1 and PD-L2 on dendritic cells augments expansion and function of minor histocompatibility antigen-specific CD8+ T cells. Blood 116:4501–4511

    Article  CAS  PubMed  Google Scholar 

  44. Roeven MW, Hobo W, van der Voort R, Fredrix H, Norde WJ, Teijgeler K, Ruiters MH, Schaap N, Dolstra H (2015) Efficient nontoxic delivery of PD-L1 and PD-L2 siRNA into dendritic cell vaccines using the cationic lipid SAINT-18. J Immunother 38:145–154

    Article  CAS  PubMed  Google Scholar 

  45. Van den Bergh JMJ, Smits ELJM, Berneman ZN, Hutten TJA, De Reu H, Van Tendeloo VFI, Dolstra H, Lion E, Hobo W (2017) Monocyte-derived dendritic cells with silenced PD-1 ligands and transpresenting interleukin-15 stimulate strong tumor-reactive T-cell expansion. Cancer Immunol Res 5:710–715

    Article  PubMed  CAS  Google Scholar 

  46. Kubo M, Handa T, Yoshimura A (2003) Suppressors of cytokine signaling and immunity. Nat Immunol 4:1169–1176

    Article  CAS  PubMed  Google Scholar 

  47. Shen L, Evel-Kabler K, Strube R, Chen SY (2004) Silencing of SOCS1 enhances antigen presentation by dendritic cells and antigen-specific anti-tumor immunity. Nat Biotechnol 22:1546–1552

    Article  CAS  PubMed  Google Scholar 

  48. Subramanya S, Armant M, Salkowitz JR (2010) Enhanced induction of HIV-specific cytotoxic T lymphocytes by dendritic cell-tar geted delivery of SOCS-1 siRNA. Mol Ther 10:2028–2037

    Article  CAS  Google Scholar 

  49. Wang D, Huang XF, Hong B, Song XT, Hu L, Jiang M, Zhang B et al (2018) Efficacy of intracellular immune checkpoint-silenced DC vaccine. JCI Insight 3. https://doi.org/10.1172/jci.insight.98368.

  50. Short NJ, Rytting ME, Cortes JE (2018) Acute myeloid leukaemia. Lancet 392:593–606

    Article  PubMed  Google Scholar 

  51. Wölfe SJ, Strebovsky J, Bartz H et al (2011) PD-L1 expression on tolerogenic APCs is controlled by STAT-3. Eur J Immunol 41:413–424

    Article  CAS  Google Scholar 

  52. Alshansan A, Haddadi A, Hamdy S et al (2010) STAT3 silencing in dendritic cells by siRNA polyplexes encapsulated in PLGA nanoparticles for the modulation of anticancer immune response. Mol Pharm 7:1643–1654

    Article  CAS  Google Scholar 

  53. Guo C, Yi H, Yu X, Zuo D, Qian J, Yang G, Foster BA, Subjeck JR, Sun X, Mikkelsen RB, Fisher PB, Wang XY (2012) In situ Vaccination with CD204 gene-silenced dendritic cell, not unmodified dendritic cell, enhances radiation therapy. Mol Cancer Ther 11:2331–2339

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Mobergslien A, Sioud M (2012) Galectin-1 and -3 gene silencing in immature and mature dendritic cells enhances T cell activation and interferon-γ production. J Leucocyte Biol 91:461–467

    Article  CAS  Google Scholar 

  55. Chen HY, Fermin A, Vardhana S, Weng IC, Lo KF, Chang EY, Maverakis E, Yang RY, Hsu DK, Dustin ML, Liu FT (2009) Galectin-3 negatively regulates TCR-mediated CD4+ T-cell activation at the immunological synapse. Proc Natl Acad Sci USA 106:14496–14501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Grossman Z, Singer A (1996) Tuning of activation threshold explains flexibility in the selection and development of T cells in the thymus. Proc Natl Acad Sci USA 93:14747–14752

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Mittal SK, Roche PA (2015) Suppression of antigen presentation by IL-10. Curr Opin Immunol 34:22–27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Reis e Sousa C (2004) Toll-like receptors and dendritic cells: for whom the bug tolls. Semin Immunol 16:27–34

    Article  CAS  PubMed  Google Scholar 

  59. Jonuleit H, Schmitt E, Schuler G, Knop J, Enk AH (2000) Induction of interleukin 10-producing, nonproliferating CD4(+) T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. J Exp Med 192:1213–1222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Sioud M (2005) Induction of inflammatory cytokines and interferon responses by double-stranded and single-stranded siRNAs is sequence-dependent and requires endosomal localization. J Mol Biol 348:1079–1010

    Article  CAS  PubMed  Google Scholar 

  61. Kleinman ME, Yamada K, Takeda A, Chandrasekaran V, Nozaki M, Baffi JZ et al (2008) Sequence- and target-independent angiogenesis suppression by siRNA via TLR3. Nature 452:591–597

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Sioud M (2006). Single-stranded small interfering RNA are more immunostimulatory than their double-stranded counterparts: a central role for 2′-hydroxyl uridines in immune responses. Eur J Immunol 36:1222–1230

    Article  CAS  PubMed  Google Scholar 

  63. Cekaite L, Furset G, Hovig E, Sioud M (2007) Gene expression analysis in blood cells in response to unmodified and 2′-modified siRNAs reveals TLR-dependent and independent effects. J Mol Biol 365:90–108

    Article  CAS  PubMed  Google Scholar 

  64. Sioud M, Furset G, Cekaite L (2007) Suppression of immunostimulatory siRNA-driven innate immune activation by 2′-modified RNAs. Biochem Biophys Res Commun 36:122–126

    Article  CAS  PubMed  Google Scholar 

  65. Hornung V, Guenthner-Biller M, Bourquin C et al (2005) Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7. Nat Med 11:263–270

    Article  CAS  PubMed  Google Scholar 

  66. Judge AD, Sood V, Shaw JR, Fang D, McClintock K, MacLachlan I (2005) Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA. Nat Biotechnol 23:457–462

    Article  CAS  PubMed  Google Scholar 

  67. Furset G, Sioud M (2007) Design of bifunctional siRNAs: combining immunostimulation and gene-silencing in one single siRNA molecule. Biochem Biophys Res Comm 352:642–649

    Article  CAS  PubMed  Google Scholar 

  68. Iversen PO, Semaeva E, Sørensen DR, Wiig H, Sioud M (2009) Dendritic cells loaded with tumor antigens and a dual immunostimulatory and anti-interleukin 10-specific small interference RNA prime T lymphocytes against leukemic cells. Transl Oncol 2:242–246

    Article  PubMed  PubMed Central  Google Scholar 

  69. Campbell JD (2017) Development of the CpG Adjuvant 1018: a case study. Methods Mol Biol 1494:15–27

    Article  CAS  PubMed  Google Scholar 

  70. Pradhan P, Qin H, Leleux JA, Gwak D, Sakamaki I, Kwak LW, Roy K (2014) The effect of combined IL10 siRNA and CpG ODN as pathogen-mimicking microparticles on Th1Th2 cytokine balance in dendritic cells and protective immunity against B cell lymphoma. Biomaterials 35:5491–5504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Chhabra A, Chakraborty NG, Mukherji B (2008) Silencing of endogenous IL-10 in human dendritic cells leads to the generation of an improved CTL response against human melanoma associated antigenic epitope, MART-127-35. Clin Immunol 126:251–259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Ahn YH, Hong SO, Kim JH, Noh KH, Song KH, Lee YH, Jeon JH, Kim DW, Seo JH, Kim TW (2015) The siRNA cocktail targeting interleukin 10 receptor and transforming growth factor-β receptor on dendritic cells potentiates tumour antigen-specific CD8+ T cell immunity. Clin Exp Immunol 181:164–178

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Kim JH, Kang TH, Noh KH et al (2011) Blocking the immunosuppressive axis with small interfering RNA targeting interleukin 10 receptor enhances dendritic cell-based vaccine potency. Clin Exp Immunol 165:180–189

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Castello L, Sabation M, Ren J, Terabe M, Khuu H, Wood LV et al (2017) Expression of CD14, IL10, and tolerogenic signature in dendritic cells inversely correlate with clinical and immunologic response to TARP vaccination in prostate cancer patients. Clin Cancer Res 23:3352–3364

    Article  CAS  Google Scholar 

  75. Van den Eynde BJ, Morel S (2001) Differential processing of class-I-restricted epitopes by the standard proteasome and the immunoproteasome. Curr Opin Immunol 13:147–153

    Article  PubMed  Google Scholar 

  76. Heink S, Fricke B, Ludwig D, Kloetzel PM, Kruger E (2006) Tumor cell lines expressing the proteasome subunit isoform LMP7E1 exhibited immunoproteasome deficiency. Cancer Res 66:649–652

    Article  CAS  PubMed  Google Scholar 

  77. Dannull J, Lesher D-T, Holzknecht R, Qi W, Hanna G, Seigler H, Tyler DS, Pruitt SK (2007) Immunoproteasome down-regulation enhances the ability of dendritic cells to stimulate antitumor immunity. Blood 110:4341–4350

    Article  CAS  PubMed  Google Scholar 

  78. Dannull J, Haley NR, Archer G, Nair S, Boczkowski D, Harper M, De Rosa N et al (2013) Melanoma immunotherapy using mature DCs expressing the constitutive proteasome. J Clin Invest 123:3135–3145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Rosenberg SA, Restifo NP, Yang JC, Morgan RA, Dudley ME (2008) Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nat Rev Cancer 8:299–330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. June CH (2007) Adoptive T cell therapy for cancer in the clinic. J Clin Invest 117:1466–1476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Hout R, Schultz LM, Marabelle A, Kohrt H (2015) T-cell-based immunotherapy: adoptive cell transfer and checkpoint inhibition. Cancer Immunol Res 3:1115–1122

    Article  CAS  Google Scholar 

  82. Mantei A, Rutz S, Janke M et al (2008) siRNA stabilization prolongs gene knockdown in primary T lymphocytes. Eur J Immunol 38:2616–2625

    Article  CAS  PubMed  Google Scholar 

  83. Freeley M, Long A (2013) The two hit hypothesis: an improved method for siRNA-mediated gene silencing in stimulated primary human T cells. J Immunol Methods 396:116–127

    Article  CAS  PubMed  Google Scholar 

  84. Borkner L, Kaiser A, van de Kasteele W, Andreesen R, Mackensen A, Haanen JB, Schumacher TN, Blank C (2010) RNA interference targeting programmed death receptor-1 improves immune functions of tumor-specific T cells. Cancer Immunol Immunother 59:1173–1183

    Article  CAS  PubMed  Google Scholar 

  85. Yu Y, Wu H, Tang Z, Zang G (2009) CTLA4 silencing with siRNA promotes deviation of Th1/Th2 in chronic hepatitis B patients. Cell Mol Immunol 6:123–127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Soutschek J, Akinc A, Bramlage B, Charisse K, Constien R et al (2004) Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 432:173–178

    Article  CAS  PubMed  Google Scholar 

  87. Shmushkovich T, Monopoli KR, Homsy D, Leyfer D et al (2018) Functional features defining the efficacy of cholesterol-conjugated, self-deliverable, chemically modified siRNAs. Nucleic Acids Res 46:10905–10916

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Ligtenberg MA, Pico de Coaña Y, Shmushkovich T, Yoshimoto Y, Truxova I, Yang Y, Betancur-Boissel M, Eliseev AV, Wolfson AD, Kiessling R (2018) Self-delivering RNAi targeting PD-1 improves tumor-specific T cell functionality for adoptive cell therapy of malignant melanoma. Mol Ther 26:1482–1493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Sioud M (2014) Engineering better immunotherapies via RNA interference. Hum Vaccin Immunother 10:3165–3174

    Article  PubMed  PubMed Central  Google Scholar 

  90. Chow VA, Shadman M, Gopal AK (2018) Translating anti-CD19 CAR T-cell therapy into clinical practice for relapsed/refractory diffuse large B-cell lymphoma. Blood 132:777–781

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Simon B, Harrer D, Schuler-Thurner B, Schaft N, Schulaer G, Dörrie UU (2018) The siRNA-mediated downregulation of PD-1 alone or simultaneously with CTL-4 shows enhanced in vitro CAR-T-cell functionality for further clinical development towards the potential use in immunotherapy of melanoma. Exp Dermatol 27:769–778

    Article  CAS  PubMed  Google Scholar 

  92. Pike KA, Tremblay ML (2013) Regulating naive and memory CD8 T cell homeostasis -a role for protein tyrosine phosphatases. FEBS J 280:432–444

    Article  CAS  PubMed  Google Scholar 

  93. Jeon MS, Atfield A, Venuprasad K, Krawczyk C, Sarao R, Elly C, Yang C, Arya S, Bachmaier K et al (2004) Essential role of the E3 ubiquitin ligase Cbl-b in T cell anergy induction. Immunity 21:167–177

    Article  CAS  PubMed  Google Scholar 

  94. Hinterleitner R, Gruber T, Pfeifhofer-Obermair C, Lutz-Nicoladoni C et al (2012) Adoptive transfer of siRNA Cblb-silenced CD8+ T lymphocytes augments tumour vaccine efficacy in a B16 melanoma model. PLoS One 7:e44295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Sathish JG, Dolton G, Leroy FG, Matthews RJ (2007) Loss of Src homology region 2 domain-containing protein tyrosine phosphatase-1 increases CD8+ T cell-APC conjugate formation and is associated with enhanced in vivo CTL function. J Immunol 178:330–337

    Article  CAS  PubMed  Google Scholar 

  96. Stromnes IM, Fowler C, Casamina CC, Georgopolos CM, McAfee MS, Schmitt TM, Tan X, Kim TD, Choi I, Blattman JN et al (2012) Abrogation of Src homology region 2 domain-containing phosphatase 1 in tumor-specific T cells improves efficacy of adoptive immunotherapy by enhancing the effector function and accumulation of short-lived effector T cells in vivo. J Immunol 189:1812–1825

    Article  CAS  PubMed  Google Scholar 

  97. Kim HJ, Kim A, Miyata K, Kataoka K (2016) Recent progress in development of siRNA delivery vehicles for cancer therapy. Adv Drug Deliv Rev 104:61–77

    Article  CAS  PubMed  Google Scholar 

  98. Rajagopalan A, Berezhny A, Schrand B, Puplampu-Dove Y, Gilboa E (2017) Aptamer-targeted attenuation of Il-2 signaling in CD8+ T cells enhances antitumor immunity. Mol Ther 25:54–61

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Wang C, Lin GH, McPherson AJ, Watts TH (2009) Immune regulation by 4-1BB and 4-1BBL: complexities and challenges. Immunol Rev 229:192–215

    Article  CAS  PubMed  Google Scholar 

  100. Sioud M (2011) Promises and challenges in developing RNAi as a research toll and therapy. Methods Mol Biol 703:173–187

    Article  CAS  PubMed  Google Scholar 

  101. Dybwad A, Førre O, Natvig JB, Sioud M (1995) Structural characterization of peptides that bind synovial-fluid antibodies from RA patients—a novel strategy for identification of disease-related epitopes using a random peptide library. Clin Immunol Immunopathol 75(1):45–50

    Article  CAS  PubMed  Google Scholar 

  102. Sioud M, Kjeldsen-Kragh J, Suleyman S, Vinje O, Natvig JB, Førre O (1992) Limited heterogeneity of T cell receptor variable region gene usage in juvenile rheumatoid arthritis synovial T cells. Eur J Immunol 22:2413–2418

    Article  CAS  PubMed  Google Scholar 

  103. Dybwad A, Bogen B, Natvig JB, Førre O, Sioud M (1995) Peptide phage libraries can be an efficient tool for identifying antibody ligands for polyclonal antisera. Clin Exp Immunol 102:438–442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was supported by the Norwegian Cancer Society.

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  1. Department of Immunology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Ullernchausseen 70, Oslo, Norway

    Mouldy Sioud

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  1. Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway

    Mouldy Sioud

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Sioud, M. (2020). Unleashing the Therapeutic Potential of Dendritic and T Cell Therapies Using RNA Interference. In: Sioud, M. (eds) RNA Interference and CRISPR Technologies. Methods in Molecular Biology, vol 2115. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0290-4_15

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  • DOI: https://doi.org/10.1007/978-1-0716-0290-4_15

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-0289-8

  • Online ISBN: 978-1-0716-0290-4

  • eBook Packages: Springer Protocols

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