A phase I vaccination study with dendritic cells loaded with NY-ESO-1 and α-galactosylceramide: induction of polyfunctional T cells in high-risk melanoma patients

Kirkwood JM, Strawderman MH, Ernstoff MS, Smith TJ, Borden EC, Blum RH (1996) Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. J Clin Oncol 14(1):7–17 Lens MB, Dawes M (2002) Interferon alfa therapy for malignant melanoma: a systematic review of randomized controlled trials. J Clin Oncol 20(7):1818–1825 Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363(8):711–723. https://doi.org/10.1056/NEJMoa1003466 Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, Ferrucci PF, Hill A, Wagstaff J, Carlino MS, Haanen JB, Maio M, Marquez-Rodas I, McArthur GA, Ascierto PA, Long GV, Callahan MK, Postow MA, Grossmann K, Sznol M, Dreno B, Bastholt L, Yang A, Rollin LM, Horak C, Hodi FS, Wolchok JD (2015) Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 373(1):23–34 Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, Hassel JC, Rutkowski P, McNeil C, Kalinka-Warzocha E, Savage KJ, Hernberg MM, Lebbe C, Charles J, Mihalcioiu C, Chiarion-Sileni V, Mauch C, Cognetti F, Arance A, Schmidt H, Schadendorf D, Gogas H, Lundgren-Eriksson L, Horak C, Sharkey B, Waxman IM, Atkinson V, Ascierto PA (2015) Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 372(4):320–330 Robert C, Thomas L, Bondarenko I, O’Day S, Weber J, Garbe C, Lebbe C, Baurain JF, Testori A, Grob JJ, Davidson N, Richards J, Maio M, Hauschild A, Miller WH Jr, Gascon P, Lotem M, Harmankaya K, Ibrahim R, Francis S, Chen TT, Humphrey R, Hoos A, Wolchok JD (2011) Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 364(26):2517–2526 Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, Hamid O, Robert C, Ascierto PA, Richards JM, Lebbe C, Ferraresi V, Smylie M, Weber JS, Maio M, Bastholt L, Mortier L, Thomas L, Tahir S, Hauschild A, Hassel JC, Hodi FS, Taitt C, de Pril V, de Schaetzen G, Suciu S, Testori A (2016) Prolonged survival in stage III melanoma with ipilimumab adjuvant therapy. N Engl J Med 375(19):1845–1855 Naidoo J, Page DB, Li BT, Connell LC, Schindler K, Lacouture ME, Postow MA, Wolchok JD (2015) Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol 26(12):2375–2391 Weber JS, Kahler KC, Hauschild A (2012) Management of immune-related adverse events and kinetics of response with ipilimumab. J Clin Oncol 30(21):2691–2697 Coffman RL, Sher A, Seder RA (2010) Vaccine adjuvants: putting innate immunity to work. Immunity 33(4):492–503. https://doi.org/10.1016/j.immuni.2010.10.002 Fujii S, Shimizu K, Smith C, Bonifaz L, Steinman RM (2003) Activation of natural killer T cells by alpha-galactosylceramide rapidly induces the full maturation of dendritic cells in vivo and thereby acts as an adjuvant for combined CD4 and CD8 T cell immunity to a coadministered protein. J Exp Med 198(2):267–279 Hermans IF, Silk JD, Gileadi U, Salio M, Mathew B, Ritter G, Schmidt R, Harris AL, Old L, Cerundolo V (2003) NKT cells enhance CD4+ and CD8+ T cell responses to soluble antigen in vivo through direct interaction with dendritic cells. J Immunol 171(10):5140–5147 Leslie DS, Vincent MS, Spada FM, Das H, Sugita M, Morita CT, Brenner MB (2002) CD1-mediated gamma/delta T cell maturation of dendritic cells. J Exp Med 196(12):1575–1584 Vincent MS, Leslie DS, Gumperz JE, Xiong X, Grant EP, Brenner MB (2002) CD1-dependent dendritic cell instruction. Nat Immunol 3(12):1163–1168. https://doi.org/10.1038/ni851 Lantz O, Bendelac A (1994) An invariant T cell receptor alpha chain is used by a unique subset of major histocompatibility complex class I-specific CD4+ and CD4−8− T cells in mice and humans. J Exp Med 180(3):1097–1106 Masuda K, Makino Y, Cui J, Ito T, Tokuhisa T, Takahama Y, Koseki H, Tsuchida K, Koike T, Moriya H, Amano M, Taniguchi M (1997) Phenotypes and invariant alpha beta TCR expression of peripheral V alpha 14 + NK T cells. J Immunol 158(5):2076–2082 Prussin C, Foster B (1997) TCR V alpha 24 and V beta 11 coexpression defines a human NK1 T cell analog containing a unique Th0 subpopulation. J Immunol 159(12):5862–5870 Mattner J, Debord KL, Ismail N, Goff RD, Cantu C 3rd, Zhou D, Saint-Mezard P, Wang V, Gao Y, Yin N, Hoebe K, Schneewind O, Walker D, Beutler B, Teyton L, Savage PB, Bendelac A (2005) Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections. Nature 434(7032):525–529. https://doi.org/10.1038/nature03408 Wu D, Xing GW, Poles MA, Horowitz A, Kinjo Y, Sullivan B, Bodmer-Narkevitch V, Plettenburg O, Kronenberg M, Tsuji M, Ho DD, Wong CH (2005) Bacterial glycolipids and analogs as antigens for CD1d-restricted NKT cells. Proc Natl Acad Sci USA 102(5):1351–1356. https://doi.org/10.1073/pnas.0408696102 Zhou D, Mattner J, Cantu C 3rd, Schrantz N, Yin N, Gao Y, Sagiv Y, Hudspeth K, Wu YP, Yamashita T, Teneberg S, Wang D, Proia RL, Levery SB, Savage PB, Teyton L, Bendelac A (2004) Lysosomal glycosphingolipid recognition by NKT cells. Science 306(5702):1786–1789. https://doi.org/10.1126/science.1103440 Akimoto K, Natori T, Morita M (1993) Synthesis and stereochemistry of agelasphin-9b. Tetrahedron Lett 34:5593–5596 Natori T, Koezuka Y, Higa T (1993) Agelasphins, novel alpha-galactosylceramides from the marine sponge agelas mauritianus. Tetrahedron Lett 34:5591–5592 Kobayashi E, Motoki K, Uchida T, Fukushima H, Koezuka Y (1995) KRN7000, a novel immunomodulator, and its antitumor activities. Oncol Res 7(10–11):529–534 Morita M, Motoki K, Akimoto K, Natori T, Sakai T, Sawa E, Yamaji K, Koezuka Y, Kobayashi E, Fukushima H (1995) Structure-activity relationship of alpha-galactosylceramides against B16-bearing mice. J Med Chem 38(12):2176–2187 Yamaguchi Y, Motoki K, Ueno H, Maeda K, Kobayashi E, Inoue H, Fukushima H, Koezuka Y (1996) Enhancing effects of (2S,3S,4R)-1-O-(alpha-d-galactopyranosyl)-2-(N-hexacosanoylamino)-1,3,4-octadecanetriol (KRN7000) on antigen-presenting function of antigen-presenting cells and antimetastatic activity of KRN7000-pretreated antigen-presenting cells. Oncol Res 8(10–11):399–407 Kitamura H, Iwakabe K, Yahata T, Nishimura S, Ohta A, Ohmi Y, Sato M, Takeda K, Okumura K, Van Kaer L, Kawano T, Taniguchi M, Nishimura T (1999) The natural killer T (NKT) cell ligand alpha-galactosylceramide demonstrates its immunopotentiating effect by inducing interleukin (IL)-12 production by dendritic cells and IL-12 receptor expression on NKT cells. J Exp Med 189(7):1121–1128 Tomura M, Yu WG, Ahn HJ, Yamashita M, Yang YF, Ono S, Hamaoka T, Kawano T, Taniguchi M, Koezuka Y, Fujiwara H (1999) A novel function of Valpha14+CD4+NKT cells: stimulation of IL-12 production by antigen-presenting cells in the innate immune system. J Immunol 163(1):93–101 Petersen TR, Sika-Paotonu D, Knight DA, Dickgreber N, Farrand KJ, Ronchese F, Hermans IF (2010) Potent anti-tumor responses to immunization with dendritic cells loaded with tumor tissue and an NKT cell ligand. Immunol Cell Biol 88(5):596–604. https://doi.org/10.1038/icb.2010.9 Chang DH, Osman K, Connolly J, Kukreja A, Krasovsky J, Pack M, Hutchinson A, Geller M, Liu N, Annable R, Shay J, Kirchhoff K, Nishi N, Ando Y, Hayashi K, Hassoun H, Steinman RM, Dhodapkar MV (2005) Sustained expansion of NKT cells and antigen-specific T cells after injection of alpha-galactosyl-ceramide loaded mature dendritic cells in cancer patients. J Exp Med 201(9):1503–1517. https://doi.org/10.1084/jem.20042592 Ishikawa A, Motohashi S, Ishikawa E, Fuchida H, Higashino K, Otsuji M, Iizasa T, Nakayama T, Taniguchi M, Fujisawa T (2005) A phase I study of alpha-galactosylceramide (KRN7000)-pulsed dendritic cells in patients with advanced and recurrent non-small cell lung cancer. Clin Cancer Res 11(5):1910–1917 Nicol AJ, Tazbirkova A, Nieda M (2011) Comparison of clinical and immunological effects of intravenous and intradermal administration of alpha-galactosylceramide (KRN7000)-pulsed dendritic cells. Clin Cancer Res 17(15):5140–5151 Nieda M, Okai M, Tazbirkova A, Lin H, Yamaura A, Ide K, Abraham R, Juji T, Macfarlane DJ, Nicol AJ (2004) Therapeutic activation of Valpha24+Vbeta11+NKT cells in human subjects results in highly coordinated secondary activation of acquired and innate immunity. Blood 103(2):383–389. https://doi.org/10.1182/blood-2003-04-1155 Jager E, Nagata Y, Gnjatic S, Wada H, Stockert E, Karbach J, Dunbar PR, Lee SY, Jungbluth A, Jager D, Arand M, Ritter G, Cerundolo V, Dupont B, Chen YT, Old LJ, Knuth A (2000) Monitoring CD8 T cell responses to NY-ESO-1: correlation of humoral and cellular immune responses. Proc Natl Acad Sci USA 97(9):4760–4765 Robbins PF, Morgan RA, Feldman SA, Yang JC, Sherry RM, Dudley ME, Wunderlich JR, Nahvi AV, Helman LJ, Mackall CL, Kammula US, Hughes MS, Restifo NP, Raffeld M, Lee CC, Levy CL, Li YF, El-Gamil M, Schwarz SL, Laurencot C, Rosenberg SA (2011) Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol 29(7):917–924 Melief CJ, van der Burg SH (2008) Immunotherapy of established (pre)malignant disease by synthetic long peptide vaccines. Nat Rev Cancer 8(5):351–360 Fujii S, Shimizu K, Kronenberg M, Steinman RM (2002) Prolonged IFN-gamma-producing NKT response induced with alpha-galactosylceramide-loaded DCs. Nat Immunol 3(9):867–874. https://doi.org/10.1038/ni827 Giaccone G, Punt CJ, Ando Y, Ruijter R, Nishi N, Peters M, von Blomberg BM, Scheper RJ, van der Vliet HJ, van den Eertwegh AJ, Roelvink M, Beijnen J, Zwierzina H, Pinedo HM (2002) A phase I study of the natural killer T-cell ligand alpha-galactosylceramide (KRN7000) in patients with solid tumors. Clin Cancer Res 8(12):3702–3709 McEwen-Smith RM, Salio M, Cerundolo V (2015) The regulatory role of invariant NKT cells in tumor immunity. Cancer Immunol Res 3(5):425–435 Snyder-Cappione JE, Tincati C, Eccles-James IG, Cappione AJ, Ndhlovu LC, Koth LL, Nixon DF (2010) A comprehensive ex vivo functional analysis of human NKT cells reveals production of MIP1-alpha and MIP1-beta, a lack of IL-17, and a Th1-bias in males. PLoS ONE 5(11):e15412 Martinuzzi E, Scotto M, Enee E, Brezar V, Ribeil JA, van Endert P, Mallone R (2008) Serum-free culture medium and IL-7 costimulation increase the sensitivity of ELISpot detection. J Immunol Methods 333(1–2):61–70. https://doi.org/10.1016/j.jim.2008.01.003 Moodie Z, Huang Y, Gu L, Hural J, Self SG (2006) Statistical positivity criteria for the analysis of ELISpot assay data in HIV-1 vaccine trials. J Immunol Methods 315(1–2):121–132 R Core Team (2015) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. http://www.r-project.org. Accessed 1 Mar 2016 Richter J, Neparidze N, Zhang L, Nair S, Monesmith T, Sundaram R, Miesowicz F, Dhodapkar KM, Dhodapkar MV (2013) Clinical regressions and broad immune activation following combination therapy targeting human NKT cells in myeloma. Blood 121(3):423–430. https://doi.org/10.1182/blood-2012-06-435503 Exley MA, Hou R, Shaulov A, Tonti E, Dellabona P, Casorati G, Akbari O, Akman HO, Greenfield EA, Gumperz JE, Boyson JE, Balk SP, Wilson SB (2008) Selective activation, expansion, and monitoring of human iNKT cells with a monoclonal antibody specific for the TCR alpha-chain CDR3 loop. Eur J Immunol 38(6):1756–1766 Gibney GT, Kudchadkar RR, DeConti RC, Thebeau MS, Czupryn MP, Tetteh L, Eysmans C, Richards A, Schell MJ, Fisher KJ, Horak CE, Inzunza HD, Yu B, Martinez AJ, Younos I, Weber JS (2015) Safety, correlative markers, and clinical results of adjuvant nivolumab in combination with vaccine in resected high-risk metastatic melanoma. Clin Cancer Res 21(4):712–720 Krishnadas DK, Shusterman S, Bai F, Diller L, Sullivan JE, Cheerva AC, George RE, Lucas KG (2015) A phase I trial combining decitabine/dendritic cell vaccine targeting MAGE-A1, MAGE-A3 and NY-ESO-1 for children with relapsed or therapy-refractory neuroblastoma and sarcoma. Cancer Immunol Immunother 64(10):1251–1260 Chen JL, Dawoodji A, Tarlton A, Gnjatic S, Tajar A, Karydis I, Browning J, Pratap S, Verfaille C, Venhaus RR, Pan L, Altman DG, Cebon JS, Old LL, Nathan P, Ottensmeier C, Middleton M, Cerundolo V (2015) NY-ESO-1 specific antibody and cellular responses in melanoma patients primed with NY-ESO-1 protein in ISCOMATRIX and boosted with recombinant NY-ESO-1 fowlpox virus. Int J Cancer 136(6):E590–E601 Dhodapkar MV, Steinman RM, Sapp M, Desai H, Fossella C, Krasovsky J, Donahoe SM, Dunbar PR, Cerundolo V, Nixon DF, Bhardwaj N (1999) Rapid generation of broad T-cell immunity in humans after a single injection of mature dendritic cells. J Clin Invest 104(2):173–180 Bijker MS, van den Eeden SJ, Franken KL, Melief CJ, van der Burg SH, Offringa R (2008) Superior induction of anti-tumor CTL immunity by extended peptide vaccines involves prolonged, DC-focused antigen presentation. Eur J Immunol 38(4):1033–1042 Seder RA, Darrah PA, Roederer M (2008) T-cell quality in memory and protection: implications for vaccine design. Nat Rev Immunol 8(4):247–258 Yuan J, Gnjatic S, Li H, Powel S, Gallardo HF, Ritter E, Ku GY, Jungbluth AA, Segal NH, Rasalan TS, Manukian G, Xu Y, Roman RA, Terzulli SL, Heywood M, Pogoriler E, Ritter G, Old LJ, Allison JP, Wolchok JD (2008) CTLA-4 blockade enhances polyfunctional NY-ESO-1 specific T cell responses in metastatic melanoma patients with clinical benefit. Proc Natl Acad Sci USA 105(51):20410–20415 Berinstein NL, Karkada M, Oza AM, Odunsi K, Villella JA, Nemunaitis JJ, Morse MA, Pejovic T, Bentley J, Buyse M, Nigam R, Weir GM, MacDonald LD, Quinton T, Rajagopalan R, Sharp K, Penwell A, Sammatur L, Burzykowski T, Stanford MM, Mansour M (2015) Survivin-targeted immunotherapy drives robust polyfunctional T cell generation and differentiation in advanced ovarian cancer patients. Oncoimmunology 4(8):e1026529 Lin Y, Gallardo HF, Ku GY, Li H, Manukian G, Rasalan TS, Xu Y, Terzulli SL, Old LJ, Allison JP, Houghton AN, Wolchok JD, Yuan J (2009) Optimization and validation of a robust human T-cell culture method for monitoring phenotypic and polyfunctional antigen-specific CD4 and CD8 T-cell responses. Cytotherapy 11(7):912–922 Sabado RL, Pavlick A, Gnjatic S, Cruz CM, Vengco I, Hasan F, Spadaccia M, Darvishian F, Chiriboga L, Holman RM, Escalon J, Muren C, Escano C, Yepes E, Sharpe D, Vasilakos JP, Rolnitzsky L, Goldberg JD, Mandeli J, Adams S, Jungbluth A, Pan L, Venhaus R, Ott PA, Bhardwaj N (2015) Resiquimod as an immunologic adjuvant for NY-ESO-1 protein vaccination in patients with high-risk melanoma. Cancer Immunol Res 3(3):278–287