Skip to main content
SpringerLink
Log in

Melanoma Vaccines

  • Chapter
  • First Online:
Targeted Therapeutics in Melanoma

Part of the book series: Current Clinical Oncology ((CCO))

  • 794 Accesses

Abstract

Many vaccines have been very successful. They can protect from many different infectious diseases, and thus contribute enormously to public health. The majority of successful vaccines induce neutralizing antibodies, which are essential for protection from disease, by the inhibition of microbe invasion and spread through the body, via extracellular compartments, or by neutralization of toxins. In contrast to infectious diseases, the pathological process in cancer is primarily intracellular. Immunity to cancer depends mainly on T cells which are capable of identifying and eliminating abnormal cells, via recognition of peptide antigens presented by major histocompatibility complex molecules at the cell surface. In some instances, tumor-specific antibodies can contribute to immune defense against cancer. Unfortunately, for many solid tumors (including melanoma), this mechanism is insufficient. Nevertheless, the search for cancer-neutralizing antibodies continues, similar to, e.g., HIV neutralizing antibodies. In this chapter, we focus on the development of T cell vaccines, a great challenge but also a promising approach as a new therapy for melanoma, other cancers, and intracellular pathogens.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Adamina M, Rosenthal R, Weber WP, Frey DM, Viehl CT, Bolli M, et al. Intranodal immunization with a vaccinia virus encoding multiple antigenic epitopes and costimulatory molecules in metastatic melanoma. Mol Ther. 2010;18:651–9.

    PubMed  CAS  Google Scholar 

  2. Adams S, O’Neill D, Bhardwaj N. Maturation matters: importance of maturation for antitumor immunity of dendritic cell vaccines. J Clin Oncol. 2004;22:3834–5; author reply 3835.

    PubMed  Google Scholar 

  3. Adams S, O’Neill DW, Nonaka D, Hardin E, Chiriboga L, Siu K, et al. Immunization of malignant melanoma patients with full-length NY-ESO-1 protein using TLR7 agonist imiquimod as vaccine adjuvant. J Immunol. 2008;181:776–84.

    PubMed  CAS  Google Scholar 

  4. Alexander-Miller MA, Leggatt GR, Berzofsky JA. Selective expansion of high- or low-avidity cytotoxic T lymphocytes and efficacy for adoptive immunotherapy. Proc Natl Acad Sci USA. 1996;93:4102–7.

    PubMed  CAS  Google Scholar 

  5. Almeida JR, Price DA, Papagno L, Arkoub ZA, Sauce D, Bornstein E, et al. Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover. J Exp Med. 2007;204:2473–85.

    PubMed  CAS  Google Scholar 

  6. Altman JD, Moss PAH, Goulder PJR, Barouch DH, McHeyzer-Williams MG, Bell JI, et al. Phenotypic analysis of antigen-specific T lymphocytes. Science. 1996;274:94–6.

    PubMed  CAS  Google Scholar 

  7. Appay V, Douek DC, Price DA. CD8+ T cell efficacy in vaccination and disease. Nat Med. 2008;14:623–8.

    PubMed  CAS  Google Scholar 

  8. Banchereau J, Ueno H, Dhodapkar M, Connolly J, Finholt JP, Klechevsky E, et al. Immune and clinical outcomes in patients with stage IV melanoma vaccinated with peptide-pulsed dendritic cells derived from CD34+ progenitors and activated with type I interferon. J Immunother. 2005;28:505–16.

    PubMed  CAS  Google Scholar 

  9. Baumgaertner P, Rufer N, Devevre E, Derre L, Rimoldi D, Geldhof C, et al. Ex vivo detectable human CD8 T-cell responses to cancer-testis antigens. Cancer Res. 2006;66:1912–6.

    PubMed  CAS  Google Scholar 

  10. Belli F, Testori A, Rivoltini L, Maio M, Andreola G, Sertoli MR, et al. Vaccination of metastatic melanoma patients with autologous tumor-derived heat shock protein gp96-peptide complexes: clinical and immunologic findings. J Clin Oncol. 2002;20:4169–80.

    PubMed  CAS  Google Scholar 

  11. Bennaceur K, Chapman J, Brikci-Nigassa L, Sanhadji K, Touraine JL, Portoukalian J. Dendritic cells dysfunction in tumour environment. Cancer Lett. 2008;272:186–96.

    PubMed  CAS  Google Scholar 

  12. Bennett MS, Ng HL, Dagarag M, Ali A, Yang OO. Epitope-dependent avidity thresholds for cytotoxic T-lymphocyte clearance of virus-infected cells. J Virol. 2007;81:4973–80.

    PubMed  CAS  Google Scholar 

  13. Berger C, Jensen MC, Lansdorp PM, Gough M, Elliott C, Riddell SR. Adoptive transfer of effector CD8+ T cells derived from central memory cells establishes persistent T cell memory in primates. J Clin Invest. 2008;118:294–305.

    PubMed  CAS  Google Scholar 

  14. Betts MR, Nason MC, West SM, De Rosa SC, Migueles SA, Abraham J, et al. HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells. Blood. 2006;107:4781–9.

    PubMed  CAS  Google Scholar 

  15. Beutler B. Inferences, questions and possibilities in Toll-like receptor signalling. Nature. 2004;430:257–63.

    PubMed  CAS  Google Scholar 

  16. Birkholz K, Schwenkert M, Kellner C, Gross S, Fey G, Schuler-Thurner B, et al. Targeting of DEC-205 on human dendritic cells results in efficient MHC class II-restricted antigen presentation. Blood. 2010;116:2277–85.

    PubMed  CAS  Google Scholar 

  17. Bonehill A, Van Nuffel AM, Corthals J, Tuyaerts S, Heirman C, Francois V, 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. 2009;15:3366–75.

    PubMed  CAS  Google Scholar 

  18. Brandmaier AG, Leitner WW, Ha SP, Sidney J, Restifo NP, Touloukian CE. High-avidity autoreactive CD4+ T cells induce host CTL, overcome Tregs and mediate tumor destruction. J Immunother. 2009;32:677–88.

    PubMed  Google Scholar 

  19. Bronte V, Apolloni E, Cabrelle A, Ronca R, Serafini P, Zamboni P, et al. Identification of a CD11b(+)/Gr-1(+)/CD31(+) myeloid progenitor capable of activating or suppressing CD8(+) T cells. Blood. 2000;96:3838–46.

    PubMed  CAS  Google Scholar 

  20. Brooks DG, Lee AM, Elsaesser H, McGavern DB, Oldstone MB. IL-10 blockade facilitates DNA vaccine-induced T cell responses and enhances clearance of persistent virus infection. J Exp Med. 2008;205:533–41.

    PubMed  CAS  Google Scholar 

  21. Butterfield LH, Comin-Anduix B, Vujanovic L, Lee Y, Dissette VB, Yang JQ, et al. Adenovirus MART-1-engineered autologous dendritic cell vaccine for metastatic melanoma. J Immunother. 2008;31:294–309.

    PubMed  Google Scholar 

  22. Butz EA, Bevan MJ. Massive expansion of antigen-specific CD8+ T cells during an acute virus infection. Immunity. 1998;8:167–75.

    PubMed  CAS  Google Scholar 

  23. Cambier J. Immunosenescence: a problem of lymphopoiesis, homeostasis, microenvironment, and signaling. Immunol Rev. 2005;205:5–6.

    PubMed  Google Scholar 

  24. Cassaday RD, Sondel PM, King DM, Macklin MD, Gan J, Warner TF, et al. A phase I study of immunization using particle-mediated epidermal delivery of genes for gp100 and GM-CSF into uninvolved skin of melanoma patients. Clin Cancer Res. 2007;13:540–9.

    PubMed  CAS  Google Scholar 

  25. Chapman PB, Morrissey DM, Panageas KS, Hamilton WB, Zhan C, Destro AN, et al. Induction of antibodies against GM2 ganglioside by immunizing melanoma patients using GM2-keyhole limpet hemocyanin  +  QS21 vaccine: a dose-response study. Clin Cancer Res. 2000;6:874–9.

    PubMed  CAS  Google Scholar 

  26. Chattopadhyay PK, Yu J, Roederer M. Live-cell assay to detect antigen-specific CD4+ T-cell responses by CD154 expression. Nat Protoc. 2006;1:1–6.

    PubMed  CAS  Google Scholar 

  27. Cheever MA, Higano C. PROVENGE (Sipuleucel-T) in prostate cancer: the first FDA approved therapeutic cancer vaccine. Clin Cancer Res. 2011;17:3520–6.

    PubMed  Google Scholar 

  28. Chianese-Bullock KA, Pressley J, Garbee C, Hibbitts S, Murphy C, Yamshchikov G, et al. MAGE-A1-, MAGE-A10-, and gp100-derived peptides are immunogenic when combined with granulocyte-macrophage colony-stimulating factor and montanide ISA-51 adjuvant and administered as part of a multipeptide vaccine for melanoma. J Immunol. 2005;174:3080–6.

    PubMed  CAS  Google Scholar 

  29. Connerotte T, Van Pel A, Godelaine D, Tartour E, Schuler-Thurner B, Lucas S, et al. Functions of Anti-MAGE T-cells induced in melanoma patients under different vaccination modalities. Cancer Res. 2008;68:3931–40.

    PubMed  CAS  Google Scholar 

  30. Cui W, Kaech SM. Generation of effector CD8+ T cells and their conversion to memory T cells. Immunol Rev. 2010;236:151–66.

    PubMed  CAS  Google Scholar 

  31. Czerkinsky C, Andersson G, Ekre HP, Nillson LA, Klareskog L, Ouchterlony O. Reverse ELISPOT assay for clonal analysis of cytokine production. I. Enumeration of gamma-interferon-secreting cells. J Immunol Methods. 1988;110:29–36.

    PubMed  CAS  Google Scholar 

  32. Dangoor A, Lorigan P, Keilholz U, Schadendorf D, Harris A, Ottensmeier C, et al. Clinical and immunological responses in metastatic melanoma patients vaccinated with a high-dose poly-epitope vaccine. Cancer Immunol Immunother. 2010;59:863–73.

    PubMed  CAS  Google Scholar 

  33. Daucher M, Price DA, Brenchley JM, Lamoreaux L, Metcalf JA, Rehm C, et al. Virological outcome after structured interruption of antiretroviral therapy for human immunodeficiency virus infection is associated with the functional profile of virus-specific CD8+ T cells. J Virol. 2008;82:4102–14.

    PubMed  CAS  Google Scholar 

  34. Davis ID, Chen W, Jackson H, Parente P, Shackleton M, Hopkins W, et al. Recombinant NY-ESO-1 protein with ISCOMATRIX adjuvant induces broad integrated antibody and CD4(+) and CD8(+) T cell responses in humans. Proc Natl Acad Sci USA. 2004;101:10697–702.

    PubMed  CAS  Google Scholar 

  35. Day CL, Kaufmann DE, Kiepiela P, Brown JA, Moodley ES, Reddy S, et al. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature. 2006;443:350–4.

    PubMed  CAS  Google Scholar 

  36. Derby M, Alexander-Miller M, Tse R, Berzofsky J. High-avidity CTL exploit two complementary mechanisms to provide better protection against viral infection than low-avidity CTL. J Immunol. 2001;166:1690–7.

    PubMed  CAS  Google Scholar 

  37. Derre L, Rivals JP, Jandus C, Pastor S, Rimoldi D, Romero P, et al. BTLA mediates inhibition of human tumor-specific CD8+ T cells that can be partially reversed by vaccination. J Clin Invest. 2010;120:157–67.

    PubMed  CAS  Google Scholar 

  38. Eggermont AM. Therapeutic vaccines in solid tumours: can they be harmful? Eur J Cancer. 2009;45:2087–90.

    PubMed  CAS  Google Scholar 

  39. Eggermont AM, Suciu S, Ruka W, Marsden J, Testori A, Corrie P, et al. EORTC 18961: post-operative adjuvant ganglioside GM2-KLH21 vaccination treatment vs observation in stage II (T3-T4N0M0) melanoma: 2nd interim analysis led to an early disclosure of the results. J Clin Oncol. 2008;26: [abstr 9004].

    Google Scholar 

  40. Epaulard O, Derouazi M, Margerit C, Marlu R, Filopon D, Polack B, et al. Optimization of a type III secretion system-based Pseudomonas aeruginosa live vector for antigen delivery. Clin Vaccine Immunol. 2008;15:308–13.

    PubMed  CAS  Google Scholar 

  41. Ernst B, Lee DS, Chang JM, Sprent J, Surh CD. The peptide ligands mediating positive selection in the thymus control T cell survival and homeostatic proliferation in the periphery. Immunity. 1999;11:173–81.

    PubMed  CAS  Google Scholar 

  42. Eton O, Kharkevitch DD, Gianan MA, Ross MI, Itoh K, Pride MW, et al. Active immunotherapy with ultraviolet B-irradiated autologous whole melanoma cells plus DETOX in patients with metastatic melanoma. Clin Cancer Res. 1998;4:619–27.

    PubMed  CAS  Google Scholar 

  43. Franco JL, Ghosh P, Wiltrout RH, Carter CR, Zea AH, Momozaki N, et al. Partial degradation of T-cell signal transduction molecules by contaminating granulocytes during protein extraction of splenic T cells from tumor-bearing mice. Cancer Res. 1995;55:3840–6.

    PubMed  CAS  Google Scholar 

  44. Frankenburg S, Elias O, Gelbart Y, Drize O, Lotem M, Ingber A, et al. Recombinant hydrophilic human gp100: uptake by dendritic cells and stimulation of autologous CD8+ lymphocytes from melanoma patients. Immunol Lett. 2004;94:253–9.

    PubMed  CAS  Google Scholar 

  45. Freeman GJ, Wherry EJ, Ahmed R, Sharpe AH. Reinvigorating exhausted HIV-specific T cells via PD-1-PD-1 ligand blockade. J Exp Med. 2006;203:2223–7.

    PubMed  CAS  Google Scholar 

  46. Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol. 2009;9:162–74.

    PubMed  CAS  Google Scholar 

  47. Gallimore A, Dumrese T, Hengartner H, Zinkernagel RM, Rammensee HG. Protective immunity does not correlate with the hierarchy of virus-specific cytotoxic T cell responses to naturally processed peptides. J Exp Med. 1998;187:1647–57.

    PubMed  CAS  Google Scholar 

  48. Germain RN. An innately interesting decade of research in immunology. Nat Med. 2004;10:1307–20.

    PubMed  CAS  Google Scholar 

  49. Ginsberg BA, Gallardo HF, Rasalan TS, Adamow M, Mu Z, Tandon S, et al. Immunologic response to xenogeneic gp100 DNA in melanoma patients: comparison of particle-mediated epidermal delivery with intramuscular injection. Clinical Cancer Res. 2010;16:4057–65.

    CAS  Google Scholar 

  50. Gnjatic S, Nishikawa H, Jungbluth AA, Gure AO, Ritter G, Jager E, et al. NY-ESO-1: review of an immunogenic tumor antigen. Adv Cancer Res. 2006;95:1–30.

    PubMed  CAS  Google Scholar 

  51. Grunebach F, Erndt S, Hantschel M, Heine A, Brossart P. Generation of antigen-specific CTL responses using RGS1 mRNA transfected dendritic cells. Cancer Immunol Immunother. 2008;57:1483–91.

    PubMed  Google Scholar 

  52. Hadrup SR, Bakker AH, Shu CJ, Andersen RS, van Veluw J, Hombrink P, et al. Parallel detection of antigen-specific T-cell responses by multidimensional encoding of MHC multimers. Nat Methods. 2009;6:520–6.

    PubMed  CAS  Google Scholar 

  53. Hadrup SR, Strindhall J, Kollgaard T, Seremet T, Johansson B, Pawelec G, et al. Longitudinal studies of clonally expanded CD8 T cells reveal a repertoire shrinkage predicting mortality and an increased number of dysfunctional cytomegalovirus-specific T cells in the very elderly. J Immunol. 2006;176:2645–53.

    PubMed  CAS  Google Scholar 

  54. Hamid O, Solomon JC, Scotland R, Garcia M, Sian S, Ye W, et al. Alum with interleukin-12 augments immunity to a melanoma peptide vaccine: correlation with time to relapse in patients with resected high-risk disease. Clinical Cancer Res. 2007;13:215–22.

    CAS  Google Scholar 

  55. Heemskerk B, Liu K, Dudley ME, Johnson LA, Kaiser A, Downey S, et al. Adoptive cell therapy for patients with melanoma, using tumor-infiltrating lymphocytes genetically engineered to secrete interleukin-2. Hum Gene Ther. 2008;19:496–510.

    PubMed  CAS  Google Scholar 

  56. Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711–23.

    PubMed  CAS  Google Scholar 

  57. Hsueh EC, Essner R, Foshag LJ, Ollila DW, Gammon G, O’Day SJ, et al. Prolonged survival after complete resection of disseminated melanoma and active immunotherapy with a therapeutic cancer vaccine. J Clin Oncol. 2002;20:4549–54.

    PubMed  CAS  Google Scholar 

  58. Iancu EM, Speiser DE, Rufer N. Assessing ageing of individual T lymphocytes: mission impossible? Mech Ageing Dev. 2008;129:67–78.

    PubMed  CAS  Google Scholar 

  59. Jager E, Karbach J, Gnjatic S, Neumann A, Bender A, Valmori D, et al. Recombinant vaccinia/fowlpox NY-ESO-1 vaccines induce both humoral and cellular NY-ESO-1-specific immune responses in cancer patients. Proc Natl Acad Sci USA. 2006;103:14453–8.

    PubMed  Google Scholar 

  60. Janeway Jr CA, Medzhitov R. Innate immune recognition. Annu Rev Immunol. 2002;20:197–216.

    PubMed  CAS  Google Scholar 

  61. Jung T, Schauer U, Heusser C, Neumann C, Rieger C. Detection of intracellular cytokines by flow cytometry. J Immunol Methods. 1993;159:197–207.

    PubMed  CAS  Google Scholar 

  62. Kawabata R, Wada H, Isobe M, Saika T, Sato S, Uenaka A, et al. Antibody response against NY-ESO-1 in CHP-NY-ESO-1 vaccinated patients. Int J Cancer. 2007;120:2178–84.

    PubMed  CAS  Google Scholar 

  63. Kearney ER, Pape KA, Loh DY, Jenkins MK. Visualization of peptide-specific T cell immunity and peripheral tolerance induction in vivo. Immunity. 1994;1:327–39.

    PubMed  CAS  Google Scholar 

  64. Kedzierska K, La Gruta NL, Davenport MP, Turner SJ, Doherty PC. Contribution of T cell receptor affinity to overall avidity for virus-specific CD8+ T cell responses. Proc Natl Acad Sci USA. 2005;102:11432–7.

    PubMed  CAS  Google Scholar 

  65. Kenter GG, Welters MJ, Valentijn AR, Lowik MJ, Berends-van der Meer DM, Vloon AP, et al. Vaccination against HPV-16 oncoproteins for vulvar intraepithelial neoplasia. N Engl J Med. 2009;361:1838–47.

    PubMed  CAS  Google Scholar 

  66. Kirkwood JM, Ibrahim JG, Sosman JA, Sondak VK, Agarwala SS, Ernstoff MS, et al. High-dose interferon alfa-2b significantly prolongs relapse-free and overall survival compared with the GM2-KLH/QS-21 vaccine in patients with resected stage IIB-III melanoma: results of intergroup trial E1694/S9512/C509801. J Clin Oncol. 2001;19:2370–80.

    PubMed  CAS  Google Scholar 

  67. Klebanoff CA, Gattinoni L, Restifo NP. CD8 T-cell memory in tumor immunology and immunotherapy. Immunol Rev. 2006;211:214–24.

    PubMed  CAS  Google Scholar 

  68. Klein L, Trautman L, Psarras S, Schnell S, Siermann A, Liblau R, et al. Visualizing the course of antigen-specific CD8 and CD4 T cell responses to a growing tumor. Eur J Immunol. 2003;33:806–14.

    PubMed  CAS  Google Scholar 

  69. Knabel M, Franz TJ, Schiemann M, Wulf A, Villmow B, Schmidt B, et al. Reversible MHC multimer staining for functional isolation of T-cell populations and effective adoptive transfer. Nat Med. 2002;8:631–7.

    PubMed  CAS  Google Scholar 

  70. Kochenderfer JN, Gress RE. A comparison and critical analysis of preclinical anticancer vaccination strategies. Exp Biol Med (Maywood). 2007;232:1130–41.

    CAS  Google Scholar 

  71. Kreiter S, Diken M, Selmi A, Tureci O, Sahin U. Tumor vaccination using messenger RNA: prospects of a future therapy. Curr Opin Immunol. 2011;23(3):399–406.

    PubMed  CAS  Google Scholar 

  72. Kruit WH, Suciu S, Dreno B, Chiarion-Sileni V, Mortier L, Robert C, et al. Immunization with recombinant MAGE-A3 protein combined with adjuvant systems AS15 or AS02B in patients with unresectable and progressive metastatic cutaneous melanoma: a randomized open-label phase II study of the EORTC Melanoma Group (16032–18031). J Clin Oncol. 2008;26: [abstract 9065].

    Google Scholar 

  73. Kruit WH, van Ojik HH, Brichard VG, Escudier B, Dorval T, Dreno B, et al. Phase 1/2 study of subcutaneous and intradermal immunization with a recombinant MAGE-3 protein in patients with detectable metastatic melanoma. Int J Cancer. 2005;117:596–604.

    PubMed  CAS  Google Scholar 

  74. Kuhn AN, Diken M, Kreiter S, Selmi A, Kowalska J, Jemielity J, et al. Phosphorothioate cap analogs increase stability and translational efficiency of RNA vaccines in immature dendritic cells and induce superior immune responses in vivo. Gene Ther. 2010;17:961–71.

    PubMed  CAS  Google Scholar 

  75. Kyte JA, Kvalheim G, Lislerud K, thor Straten P, Dueland S, Aamdal S, et al. T cell responses in melanoma patients after vaccination with tumor-mRNA transfected dendritic cells. Cancer Immunol Immunother. 2007;56:659–75.

    PubMed  CAS  Google Scholar 

  76. Lai P, Rabinowich H, Crowley-Nowick PA, Bell MC, Mantovani G, Whiteside TL. Alterations in expression and function of signal-transducing proteins in tumor-associated T and natural killer cells in patients with ovarian carcinoma. Clin Cancer Res. 1996;2:161–73.

    PubMed  CAS  Google Scholar 

  77. Lang A, Brien JD, Messaoudi I, Nikolich-Zugich J. Age-related dysregulation of CD8+ T cell memory specific for a persistent virus is independent of viral replication. J Immunol. 2008;180:4848–57.

    PubMed  CAS  Google Scholar 

  78. Lichterfeld M, Yu XG, Mui SK, Williams KL, Trocha A, Brockman MA, et al. Selective depletion of high-avidity human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T cells after early HIV-1 infection. J Virol. 2007;81:4199–214.

    PubMed  CAS  Google Scholar 

  79. Lienard D, Rimoldi D, Marchand M, Dietrich PY, van Baren N, Geldhof C, et al. Ex vivo detectable activation of Melan-A-specific T cells correlating with inflammatory skin reactions in melanoma patients vaccinated with peptides in IFA. Cancer Immun. 2004;4:4.

    PubMed  Google Scholar 

  80. Lindsey KR, Gritz L, Sherry R, Abati A, Fetsch PA, Goldfeder LC, et al. Evaluation of prime/boost regimens using recombinant poxvirus/tyrosinase vaccines for the treatment of patients with metastatic melanoma. Clin Cancer Res. 2006;12:2526–37.

    PubMed  CAS  Google Scholar 

  81. Linton PJ, Dorshkind K. Age-related changes in lymphocyte development and function. Nat Immunol. 2004;5:133–9.

    PubMed  CAS  Google Scholar 

  82. Livingston PO, Wong GY, Adluri S, Tao Y, Padavan M, Parente R, et al. Improved survival in stage III melanoma patients with GM2 antibodies: a randomized trial of adjuvant vaccination with GM2 ganglioside. J Clin Oncol. 1994;12:1036–44.

    PubMed  CAS  Google Scholar 

  83. Lonchay C, van der Bruggen P, Connerotte T, Hanagiri T, Coulie P, Colau D, et al. Correlation between tumor regression and T cell responses in melanoma patients vaccinated with a MAGE antigen. Proc Natl Acad Sci USA. 2004;101 Suppl 2:14631–8.

    PubMed  CAS  Google Scholar 

  84. Markovic SN, Dietz AB, Greiner CW, Maas ML, Butler GW, Padley DJ, et al. Preparing clinical-grade myeloid dendritic cells by electroporation-mediated transfection of in vitro amplified tumor-derived mRNA and safety testing in stage IV malignant melanoma. J Transl Med. 2006;4:35.

    PubMed  Google Scholar 

  85. Mellor AL, Baban B, Chandler P, Marshall B, Jhaver K, Hansen A, et al. Cutting edge: induced indoleamine 2,3 dioxygenase expression in dendritic cell subsets suppresses T cell clonal expansion. J Immunol. 2003;171:1652–5.

    PubMed  CAS  Google Scholar 

  86. Messaoudi I, Guevara Patino JA, Dyall R, LeMaoult J, Nikolich-Zugich J. Direct link between MHC polymorphism, T cell avidity, and diversity in immune defense. Science. 2002;298:1797–800.

    PubMed  CAS  Google Scholar 

  87. Meyer RG, Britten CM, Siepmann U, Petzold B, Sagban TA, Lehr HA, et al. A phase I vaccination study with tyrosinase in patients with stage II melanoma using recombinant modified vaccinia virus Ankara (MVA-hTyr). Cancer Immunol Immunother. 2005;54:453–67.

    PubMed  CAS  Google Scholar 

  88. Michiels A, Tuyaerts S, Bonehill A, Heirman C, Corthals J, Thielemans K. Delivery of tumor-antigen-encoding mRNA into dendritic cells for vaccination. Methods Mol Biol. 2008;423:155–63.

    PubMed  CAS  Google Scholar 

  89. Miller RA. The aging immune system: primer and prospectus. Science. 1996;273:70–4.

    PubMed  CAS  Google Scholar 

  90. Mitchell MS, Kan-Mitchell J, Kempf RA, Harel W, Shau HY, Lind S. Active specific immunotherapy for melanoma: phase I trial of allogeneic lysates and a novel adjuvant. Cancer Res. 1988;48:5883–93.

    PubMed  CAS  Google Scholar 

  91. Moon JJ, Chu HH, Pepper M, McSorley SJ, Jameson SC, Kedl RM, et al. Naive CD4(+) T cell frequency varies for different epitopes and predicts repertoire diversity and response magnitude. Immunity. 2007;27:203–13.

    PubMed  CAS  Google Scholar 

  92. Morton DL, Mozzillo N, Thompson JF, Kelley MC, Faries M, Wagner J, et al. An international, randomized, phase III trial of bacillus Calmette-Guerin (BCG) plus allogeneic melanoma vaccine (MCV) or placebo after complete resection of melanoma metastatic to regional or distant sites. J Clin Oncol. 2007;25: [abstract 8508].

    Google Scholar 

  93. Murali-Krishna K, Altman JD, Suresh M, Sourdive DJ, Zajac AJ, Miller JD, et al. Counting antigen-specific CD8 T cells: a reevaluation of bystander activation during viral infection. Immunity. 1998;8:177–87.

    PubMed  CAS  Google Scholar 

  94. Murdoch C, Muthana M, Coffelt SB, Lewis CE. The role of myeloid cells in the promotion of tumour angiogenesis. Nat Rev Cancer. 2008;8:618–31.

    PubMed  CAS  Google Scholar 

  95. Nesic D, Vukmanovic S. MHC class I is required for peripheral accumulation of CD8+ thymic emigrants. J Immunol. 1998;160:3705–12.

    PubMed  CAS  Google Scholar 

  96. Nestle FO, Alijagic S, Gilliet M, Sun Y, Grabbe S, Dummer R, et al. Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat Med. 1998;4:328–32.

    PubMed  CAS  Google Scholar 

  97. Newell EW, Klein LO, Yu W, Davis MM. Simultaneous detection of many T-cell specificities using combinatorial tetramer staining. Nat Methods. 2009;6:497–9.

    PubMed  CAS  Google Scholar 

  98. Nicholaou T, Ebert LM, Davis ID, McArthur GA, Jackson H, Dimopoulos N, et al. Regulatory T-cell-mediated attenuation of T-cell responses to the NY-ESO-1 ISCOMATRIX vaccine in patients with advanced malignant melanoma. Clin Cancer Res. 2009;15:2166–73.

    PubMed  CAS  Google Scholar 

  99. Nikolich-Zugich J. Ageing and life-long maintenance of T-cell subsets in the face of latent persistent infections. Nat Rev Immunol. 2008;8:512–22.

    PubMed  CAS  Google Scholar 

  100. Obar JJ, Khanna KM, Lefrancois L. Endogenous naive CD8+ T cell precursor frequency regulates primary and memory responses to infection. Immunity. 2008;28:859–69.

    PubMed  CAS  Google Scholar 

  101. Ochoa AC, Longo DL. Alteration of signal transduction in T cells from cancer patients. Important Adv Oncol. 1995;43–54.

    Google Scholar 

  102. Odunsi K, Qian F, Matsuzaki J, Mhawech-Fauceglia P, Andrews C, Hoffman EW, et al. Vaccination with an NY-ESO-1 peptide of HLA class I/II specificities induces integrated humoral and T cell responses in ovarian cancer. Proc Natl Acad Sci USA. 2007;104:12837–42.

    PubMed  CAS  Google Scholar 

  103. Ostrand-Rosenberg S, Sinha P. Myeloid-derived suppressor cells: linking inflammation and cancer. J Immunol. 2009;182:4499–506.

    PubMed  CAS  Google Scholar 

  104. Pardoll D. Does the immune system see tumors as foreign or self? Annu Rev Immunol. 2003;21:807–39.

    PubMed  CAS  Google Scholar 

  105. Paris RM, Kim JH, Robb ML, Michael NL. Prime-boost immunization with poxvirus or adenovirus vectors as a strategy to develop a protective vaccine for HIV-1. Expert Rev Vaccines. 2010;9:1055–69.

    PubMed  CAS  Google Scholar 

  106. Pawelec G, Akbar A, Caruso C, Effros R, Grubeck-Loebenstein B, Wikby A. Is immunosenescence infectious? Trends Immunol. 2004;25:406–10.

    PubMed  CAS  Google Scholar 

  107. Peterson AC, Harlin H, Gajewski TF. Immunization with Melan-A peptide-pulsed peripheral blood mononuclear cells plus recombinant human interleukin-12 induces clinical activity and T-cell responses in advanced melanoma. J Clin Oncol. 2003;21:2342–8.

    PubMed  CAS  Google Scholar 

  108. Petrovas C, Casazza JP, Brenchley JM, Price DA, Gostick E, Adams WC, et al. PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection. J Exp Med. 2006;203:2281–92.

    PubMed  CAS  Google Scholar 

  109. Plog MS, Guyre CA, Roberts BL, Goldberg M, St George JA, Perricone MA. Preclinical safety and biodistribution of adenovirus-based cancer vaccines after intradermal delivery. Hum Gene Ther. 2006;17:705–16.

    PubMed  CAS  Google Scholar 

  110. Price DA, Brenchley JM, Ruff LE, Betts MR, Hill BJ, Roederer M, et al. Avidity for antigen shapes clonal dominance in CD8+ T cell populations specific for persistent DNA viruses. J Exp Med. 2005;202:1349–61.

    PubMed  CAS  Google Scholar 

  111. Pulendran B, Ahmed R. Translating innate immunity into immunological memory: implications for vaccine development. Cell. 2006;124:849–63.

    PubMed  CAS  Google Scholar 

  112. Pullarkat V, Lee PP, Scotland R, Rubio V, Groshen S, Gee C, et al. A phase I trial of SD-9427 (progenipoietin) with a multipeptide vaccine for resected metastatic melanoma. Clin Cancer Res. 2003;9:1301–12.

    PubMed  CAS  Google Scholar 

  113. Quaak SG, van den Berg JH, Toebes M, Schumacher TN, Haanen JB, Beijnen JH, et al. GMP production of pDERMATT for vaccination against melanoma in a phase I clinical trial. Eur J Pharm Biopharm. 2008;70:429–38.

    PubMed  CAS  Google Scholar 

  114. Rehr M, Cahenzli J, Haas A, Price DA, Gostick E, Huber M, et al. Emergence of polyfunctional CD8+ T cells after prolonged suppression of human immunodeficiency virus replication by antiretroviral therapy. J Virol. 2008;82:3391–404.

    PubMed  CAS  Google Scholar 

  115. Reyes-Sandoval A, Berthoud T, Alder N, Siani L, Gilbert SC, Nicosia A, et al. Prime-boost immunization with adenoviral and modified vaccinia virus Ankara vectors enhances the durability and polyfunctionality of protective malaria CD8+ T-cell responses. Infect Immun. 2010;78:145–53.

    PubMed  CAS  Google Scholar 

  116. Rizzuto GA, Merghoub T, Hirschhorn-Cymerman D, Liu C, Lesokhin AM, Sahawneh D, et al. Self-antigen-specific CD8+ T cell precursor frequency determines the quality of the antitumor immune response. J Exp Med. 2009;206:849–66.

    PubMed  CAS  Google Scholar 

  117. Romano E, Rossi M, Ratzinger G, de Cos MA, Chung DJ, Panageas KS, et al. Peptide-loaded langerhans cells, despite increased IL15 secretion and T-cell activation in vitro, elicit antitumor T-cell responses comparable to peptide-loaded monocyte-derived dendritic cells in vivo. Clin Cancer Res. 2011;17:1984–97.

    PubMed  CAS  Google Scholar 

  118. Romero P, Cerottini JC, Speiser DE. Monitoring tumor antigen specific T-cell responses in cancer patients and phase I clinical trials of peptide-based vaccination. Cancer Immunol Immunother. 2004;53:249–55.

    PubMed  Google Scholar 

  119. Rosenberg SA, Sherry RM, Morton KE, Scharfman WJ, Yang JC, Topalian SL, et al. Tumor progression can occur despite the induction of very high levels of self/tumor antigen-specific CD8+ T cells in patients with melanoma. J Immunol. 2005;175:6169–76.

    PubMed  CAS  Google Scholar 

  120. Rosenberg SA, Yang JC, Restifo NP. Cancer immunotherapy: moving beyond current vaccines. Nat Med. 2004;10:909–15.

    PubMed  CAS  Google Scholar 

  121. Rufer N. Molecular tracking of antigen-specific T-cell clones during immune responses. Curr Opin Immunol. 2005;17:441–7.

    PubMed  CAS  Google Scholar 

  122. Russmann H, Shams H, Poblete F, Fu Y, Galan JE, Donis RO. Delivery of epitopes by the Salmonella type III secretion system for vaccine development. Science. 1998;281:565–8.

    PubMed  CAS  Google Scholar 

  123. Schadendorf D, Ugurel S, Schuler-Thurner B, Nestle FO, Enk A, Brocker EB, et al. Dacarbazine (DTIC) versus vaccination with autologous peptide-pulsed dendritic cells (DC) in first-line treatment of patients with metastatic melanoma: a randomized phase III trial of the DC study group of the DeCOG. Ann Oncol. 2006;17:563–70.

    PubMed  CAS  Google Scholar 

  124. Schuler-Thurner B, Schultz ES, Berger TG, Weinlich G, Ebner S, Woerl P, et al. Rapid induction of tumor-specific type 1 T helper cells in metastatic melanoma patients by vaccination with mature, cryopreserved, peptide-loaded monocyte-derived dendritic cells. J Exp Med. 2002;195:1279–88.

    PubMed  CAS  Google Scholar 

  125. Schwartzentruber DJ, Lawson D, Richards J, Conry RM, Miller D, Triesman J, et al. A phase III multi-institutional randomized study of immunization with the gp, 100:209–217(210 M) peptide followed by high-dose IL-2 compared with high-dose IL-2 alone in patients with metastatic melanoma. J Clin Oncol. 2009;27: [abstr CRA9011].

    Google Scholar 

  126. Sedlik C, Dadaglio G, Saron MF, Deriaud E, Rojas M, Casal SI, et al. In vivo induction of a high-avidity, high-frequency cytotoxic T-lymphocyte response is associated with antiviral protective immunity. J Virol. 2000;74:5769–75.

    PubMed  CAS  Google Scholar 

  127. Shen X, Zhou J, Hathcock KS, Robbins P, Powell Jr DJ, Rosenberg SA, et al. Persistence of tumor infiltrating lymphocytes in adoptive immunotherapy correlates with telomere length. J Immunother. 2007;30:123–9.

    PubMed  CAS  Google Scholar 

  128. Slingluff Jr CL, Petroni GR, Chianese-Bullock KA, Smolkin ME, Hibbitts S, Murphy C, et al. Immunologic and clinical outcomes of a randomized phase II trial of two multipeptide vaccines for melanoma in the adjuvant setting. Clin Cancer Res. 2007;13:6386–95.

    PubMed  CAS  Google Scholar 

  129. Slingluff Jr CL, Petroni GR, Yamshchikov GV, Barnd DL, Eastham S, Galavotti H, et al. Clinical and immunologic results of a randomized phase II trial of vaccination using four melanoma peptides either administered in granulocyte-macrophage colony-stimulating factor in adjuvant or pulsed on dendritic cells. J Clin Oncol. 2003;21:4016–26.

    PubMed  CAS  Google Scholar 

  130. Smith CL, Dunbar PR, Mirza F, Palmowski MJ, Shepherd D, Gilbert SC, et al. Recombinant modified vaccinia Ankara primes functionally activated CTL specific for a melanoma tumor antigen epitope in melanoma patients with a high risk of disease recurrence. Int J Cancer. 2005;113:259–66.

    PubMed  CAS  Google Scholar 

  131. Smith CL, Mirza F, Pasquetto V, Tscharke DC, Palmowski MJ, Dunbar PR, et al. Immunodominance of poxviral-specific CTL in a human trial of recombinant-modified vaccinia Ankara. J Immunol. 2005;175:8431–7.

    PubMed  CAS  Google Scholar 

  132. Smith 2nd JW, Walker EB, Fox BA, Haley D, Wisner KP, Doran T, et al. Adjuvant immunization of HLA-A2-positive melanoma patients with a modified gp100 peptide induces peptide-specific CD8+ T-cell responses. J Clin Oncol. 2003;21:1562–73.

    PubMed  CAS  Google Scholar 

  133. Sondak VK, Liu PY, Tuthill RJ, Kempf RA, Unger JM, Sosman JA, et al. Adjuvant immunotherapy of resected, intermediate-thickness, node-negative melanoma with an allogeneic tumor vaccine: overall results of a randomized trial of the Southwest Oncology Group. J Clin Oncol. 2002;20:2058–66.

    PubMed  CAS  Google Scholar 

  134. Sosman JA, Unger JM, Liu PY, Flaherty LE, Park MS, Kempf RA, et al. Adjuvant immunotherapy of resected, intermediate-thickness, node-negative melanoma with an allogeneic tumor vaccine: impact of HLA class I antigen expression on outcome. J Clin Oncol. 2002;20:2067–75.

    PubMed  CAS  Google Scholar 

  135. Spaner DE, Astsaturov I, Vogel T, Petrella T, Elias I, Burdett-Radoux S, et al. Enhanced viral and tumor immunity with intranodal injection of canary pox viruses expressing the melanoma antigen, gp100. Cancer. 2006;106:890–9.

    PubMed  CAS  Google Scholar 

  136. Speiser DE. Immunological techniques: ex vivo characterization of T cell-mediated immune responses in cancer. Curr Opin Immunol. 2005;17:419–22.

    PubMed  CAS  Google Scholar 

  137. Speiser DE, Baumgaertner P, Barbey C, Rubio-Godoy V, Moulin A, Corthesy P, et al. A novel approach to characterize clonality and differentiation of human melanoma-specific T cell responses: spontaneous priming and efficient boosting by vaccination. J Immunol. 2006;177:1338–48.

    PubMed  CAS  Google Scholar 

  138. Speiser DE, Baumgaertner P, Voelter V, Devevre E, Barbey C, Rufer N, et al. Unmodified self antigen triggers human CD8 T cells with stronger tumor reactivity than altered antigen. Proc Natl Acad Sci USA. 2008;105:3849–54.

    PubMed  CAS  Google Scholar 

  139. Speiser DE, Kyburz D, Stübi U, Hengartner H, Zinkernagel RM. Discrepancy between in vitro measurable and in vivo virus neutralizing cytotoxic T cell reactivities: low T cell receptor specificity and avidity sufficient for in vitro proliferation or cytotoxicity to peptide coated target cells but not for in vivo protection. J Immunol. 1992;149:972–80.

    PubMed  CAS  Google Scholar 

  140. Speiser DE, Lienard D, Rufer N, Rubio-Godoy V, Rimoldi D, Lejeune F, et al. Rapid and strong human CD8+ T cell responses to vaccination with peptide, IFA and CpG oligodeoxynucleotide 7909. J Clin Invest. 2005;115:739–46.

    PubMed  CAS  Google Scholar 

  141. Speiser DE, Lienard D, Rufer N, Rubio-Godoy V, Rimoldi D, Lejeune F, et al. Rapid and strong human CD8+ T cell responses to vaccination with peptide, IFA, and CpG oligodeoxynucleotide 7909. J Clin Invest. 2005;115:739–46.

    PubMed  CAS  Google Scholar 

  142. Staveley-O’Carroll K, Sotomayor E, Montgomery J, Borrello I, Hwang L, Fein S, et al. Induction of antigen-specific T cell anergy: an early event in the course of tumor progression. Proc Natl Acad Sci USA. 1998;95:1178–83.

    PubMed  Google Scholar 

  143. Tacken PJ, de Vries IJ, Torensma R, Figdor CG. Dendritic-cell immunotherapy: from ex vivo loading to in vivo targeting. Nat Rev Immunol. 2007;7:790–802.

    PubMed  CAS  Google Scholar 

  144. Takeda K, Kaisho T, Akira S. Toll-like receptors. Annu Rev Immunol. 2003;21:335–76.

    PubMed  CAS  Google Scholar 

  145. Taswell C. Limiting dilution assays for the determination of immunocompetent cell frequencies. J Immunol. 1981;126:1614–9.

    PubMed  CAS  Google Scholar 

  146. Touvrey C, Derre L, Devevre E, Corthesy P, Romero P, Rufer N, et al. Dominant human CD8 T cell clonotypes persist simultaneously as memory and effector cells in memory phase. J Immunol. 2009;182:6718–26.

    PubMed  CAS  Google Scholar 

  147. Trautmann L, Janbazian L, Chomont N, Said EA, Gimmig S, Bessette B, et al. Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction. Nat Med. 2006;12:1198–202.

    PubMed  CAS  Google Scholar 

  148. Uenaka A, Wada H, Isobe M, Saika T, Tsuji K, Sato E, et al. T cell immunomonitoring and tumor responses in patients immunized with a complex of cholesterol-bearing hydrophobized pullulan (CHP) and NY-ESO-1 protein. Cancer Immun. 2007;7:9.

    PubMed  Google Scholar 

  149. Valmori D, Dutoit V, Ayyoub M, Rimoldi D, Guillaume P, Lienard D, et al. Simultaneous CD8+ T cell responses to multiple tumor antigen epitopes in a multipeptide melanoma vaccine. Cancer Immun. 2003;3:15.

    PubMed  Google Scholar 

  150. Valmori D, Souleimanian NE, Tosello V, Bhardwaj N, Adams S, O’Neill D, et al. Vaccination with NY-ESO-1 protein and CpG in Montanide induces integrated antibody/Th1 responses and CD8 T cells through cross-priming. Proc Natl Acad Sci USA. 2007;104:8947–52.

    PubMed  CAS  Google Scholar 

  151. van Baren N, Bonnet MC, Dreno B, Khammari A, Dorval T, Piperno-Neumann S, et al. Tumoral and immunologic response after vaccination of melanoma patients with an ALVAC virus encoding MAGE antigens recognized by T cells. J Clin Oncol. 2005;23:9008–21.

    PubMed  Google Scholar 

  152. Verdijk P, Aarntzen EH, Lesterhuis WJ, Boullart AC, Kok E, van Rossum MM, 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. 2009;15:2531–40.

    PubMed  CAS  Google Scholar 

  153. Walker EB, Haley D, Miller W, Floyd K, Wisner KP, Sanjuan N, et al. gp100(209-2 M) peptide immunization of human lymphocyte antigen-A2+ stage I-III melanoma patients induces significant increase in antigen-specific effector and long-term memory CD8+ T cells. Clin Cancer Res. 2004;10:668–80.

    PubMed  CAS  Google Scholar 

  154. Wehler TC, Karg M, Distler E, Konur A, Nonn M, Meyer RG, et al. Rapid identification and sorting of viable virus-reactive CD4(+) and CD8(+) T cells based on antigen-triggered CD137 expression. J Immunol Methods. 2008;339:23–37.

    PubMed  CAS  Google Scholar 

  155. Weide B, Pascolo S, Scheel B, Derhovanessian E, Pflugfelder A, Eigentler TK, et al. Direct injection of protamine-protected mRNA: results of a phase 1/2 vaccination trial in metastatic melanoma patients. J Immunother. 2009;32:498–507.

    PubMed  CAS  Google Scholar 

  156. Wherry EJ, Blattman JN, Murali-Krishna K, van der Most R, Ahmed R. Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment. J Virol. 2003;77:4911–27.

    PubMed  CAS  Google Scholar 

  157. Wherry EJ, Ha SJ, Kaech SM, Haining WN, Sarkar S, Kalia V, et al. Molecular signature of CD8+ T cell exhaustion during chronic viral infection. Immunity. 2007;27:670–84.

    PubMed  CAS  Google Scholar 

  158. Wherry EJ, Teichgraber V, Becker TC, Masopust D, Kaech SM, Antia R, et al. Lineage relationship and protective immunity of memory CD8 T cell subsets. Nat Immunol. 2003;4:225–34.

    PubMed  CAS  Google Scholar 

  159. Whiteside TL. Down-regulation of zeta-chain expression in T cells: a biomarker of prognosis in cancer? Cancer Immunol Immunother. 2004;53:865–78.

    PubMed  CAS  Google Scholar 

  160. Willimsky G, Czeh M, Loddenkemper C, Gellermann J, Schmidt K, Wust P, et al. Immunogenicity of premalignant lesions is the primary cause of general cytotoxic T lymphocyte unresponsiveness. J Exp Med. 2008;205:1687–700.

    PubMed  CAS  Google Scholar 

  161. Wolchok JD, Yuan J, Houghton AN, Gallardo HF, Rasalan TS, Wang J, et al. Safety and immunogenicity of tyrosinase DNA vaccines in patients with melanoma. Mol Ther. 2007;15:2044–50.

    PubMed  CAS  Google Scholar 

  162. Wolfl M, Kuball J, Ho WY, Nguyen H, Manley TJ, Bleakley M, et al. Activation-induced expression of CD137 permits detection, isolation, and expansion of the full repertoire of CD8+ T cells responding to antigen without requiring knowledge of epitope specificities. Blood. 2007;110:201–10.

    PubMed  CAS  Google Scholar 

  163. Wood LM, Guirnalda PD, Seavey MM, Paterson Y. Cancer immunotherapy using Listeria monocytogenes and listerial virulence factors. Immunol Res. 2008;42:233–45.

    PubMed  Google Scholar 

  164. Yee C, Savage PA, Lee PP, Davis MM, Greenberg PD. Isolation of high avidity melanoma-reactive CTL from heterogeneous populations using peptide-MHC tetramers. J Immunol. 1999;162:2227–34.

    PubMed  CAS  Google Scholar 

  165. Yewdall AW, Drutman SB, Jinwala F, Bahjat KS, Bhardwaj N. CD8+ T cell priming by dendritic cell vaccines requires antigen transfer to endogenous antigen presenting cells. PLoS One. 2010;5:e11144.

    PubMed  Google Scholar 

  166. Yi JS, Cox MA, Zajac AJ. T-cell exhaustion: characteristics, causes and conversion. Immunology. 2010;129:474–81.

    PubMed  CAS  Google Scholar 

  167. Zeh 3rd HJ, Perry-Lalley D, Dudley ME, Rosenberg SA, Yang JC. High avidity CTLs for two self-antigens demonstrate superior in vitro and in vivo antitumor efficacy. J Immunol. 1999;162:989–94.

    PubMed  CAS  Google Scholar 

  168. Zhou J, Shen X, Huang J, Hodes RJ, Rosenberg SA, Robbins PF. Telomere length of transferred lymphocytes correlates with in vivo persistence and tumor regression in melanoma patients receiving cell transfer therapy. J Immunol. 2005;175:7046–52.

    PubMed  CAS  Google Scholar 

  169. Zhu X, Zhou P, Cai J, Yang G, Liang S, Ren D. Tumor antigen delivered by Salmonella III secretion protein fused with heat shock protein 70 induces protection and eradication against murine melanoma. Cancer Sci. 2010;101:2621–8.

    PubMed  CAS  Google Scholar 

  170. Zippelius A, Batard P, Rubio-Godoy V, Bioley G, Lienard D, Lejeune F, et al. Effector function of human tumor-specific CD8 T cells in melanoma lesions: a state of local functional tolerance. Cancer Res. 2004;64:2865–73.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Therapeutic cancer vaccines, Ludwig Center for Cancer Research of the University of Lausanne, Lausanne, Switzerland

    Pedro Romero MD

  2. Ludwig Center for Cancer Research of the University of Lausanne, Lausanne, Switzerland

    Daniel E. Speiser MD

Authors
  1. Pedro Romero MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel E. Speiser MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pedro Romero MD .

Editor information

Editors and Affiliations

  1. , Pathology, University of Chicago, S. Maryland Ave. 5841, Chicago, 60637, Illinois, USA

    Thomas F. Gajewski

  2. , Melanoma Disease Center, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, 02215, Massachusetts, USA

    F. Stephen Hodi

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Romero, P., Speiser, D.E. (2012). Melanoma Vaccines. In: Gajewski, T., Hodi, F. (eds) Targeted Therapeutics in Melanoma. Current Clinical Oncology. Springer, New York, NY. https://doi.org/10.1007/978-1-61779-407-0_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-61779-407-0_12

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-61779-406-3

  • Online ISBN: 978-1-61779-407-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation