Cancer Immunology, Immunotherapy

, Volume 60, Issue 8, pp 1127–1135

Ten years of progress in vaccination against cancer: the need to counteract cancer evasion by dual targeting in future therapies

  • Yeranddy A. Alpizar
  • Benjamin Chain
  • Mary K. Collins
  • John Greenwood
  • David Katz
  • Hans J. Stauss
  • N. Avrion Mitchison
Focussed Research Review
  • 206 Downloads

Abstract

Although cancer immunology has made vigorous progress over the last decade, its future remains uncertain. Tumors have clearly proved subject to immune surveillance, leading to antigenic editing, and means of activating both T and B arms of the immune system have been devised. Therapeutic vaccination and monoclonal antibody therapy have so far proved disappointing, because tumors prove adept at evasion from immune control. Dual targeting could well counteract evasion, provided that the two targets are independent and are attacked simultaneously. This stage has nearly but not quite been reached in several forms of immunotherapy, particularly of B-cell cancers, although such treatment also carries hazards.

Keywords

Cancer Immunotherapy Progress Epidemiology Immunoediting Evasion 

References

  1. 1.
    Shankaran V, Ikeda H, Bruce AT, White JM, Swanson PE, Old LJ, Schreiber RD (2001) IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 410:1107–1111PubMedCrossRefGoogle Scholar
  2. 2.
    Koebel CM, Vermi W, Swann JB, Zerafa N, Rodig SJ, Old LJ, Smyth MJ, Schreiber RD (2007) Adaptive immunity maintains occult cancer in an equilibrium state. Nature 450:903–907PubMedCrossRefGoogle Scholar
  3. 3.
    Copier J, Dalgleish AG, Britten CM, Finke LH, Gaudernack G, Gnjatic S, Kallen K, Kiessling R, Schuessler-Lenz M, Singh H, Talmadge J, Zwierzina H, Hakansson L (2009) Improving the efficacy of cancer immunotherapy. Eur J Cancer 45:1424–1431PubMedCrossRefGoogle Scholar
  4. 4.
    Grulich AE, van Leeuwen MT, Falster MO, Vajdic CM (2007) Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet 370:59–67PubMedCrossRefGoogle Scholar
  5. 5.
    Heusinkveld M, Welters MJ, van Poelgeest MI, van der Hulst JM, Melief CJ, Fleuren GJ, Kenter GG, van der Burg SH (2010) The detection of circulating Human Papillomavirus (HPV)-specific T cells is associated with improved survival of patients with deeply infiltrating tumors. Int J CancerGoogle Scholar
  6. 6.
    Mammas IN, Sourvinos G, Zaravinos A, Spandidos DA (2010) Vaccination against human papilloma virus (HPV): epidemiological evidence of HPV in non-genital cancers. Pathol Oncol ResGoogle Scholar
  7. 7.
    Prehn RT, Main JM (1957) Immunity to methylcholanthrene-induced sarcomas. J Natl Cancer Inst 18:769–778PubMedGoogle Scholar
  8. 8.
    Fassati A, Mitchison NA (2009) Testing the theory of immune selection in cancers that break the rules of transplantation. Cancer Immunol Immunother 59:643–651PubMedCrossRefGoogle Scholar
  9. 9.
    Boon T, Coulie PG, Van den Eynde BJ, van der Bruggen P (2006) Human T cell responses against melanoma. Annu Rev Immunol 24:175–208PubMedCrossRefGoogle Scholar
  10. 10.
    Speiser DE, Pittet MJ, Rimoldi D, Guillaume P, Luescher IF, Lienard D, Lejeune F, Cerottini JC, Romero P (2003) Evaluation of melanoma vaccines with molecularly defined antigens by ex vivo monitoring of tumor-specific T cells. Semin Cancer Biol 13:461–472PubMedCrossRefGoogle Scholar
  11. 11.
    Carretero R, Romero JM, Ruiz-Cabello F, Maleno I, Rodriguez F, Camacho FM, Real LM, Garrido F, Cabrera T (2008) Analysis of HLA class I expression in progressing and regressing metastatic melanoma lesions after immunotherapy. Immunogenetics 60:439–447PubMedCrossRefGoogle Scholar
  12. 12.
    Chang CC, Ferrone S (2007) Immune selective pressure and HLA class I antigen defects in malignant lesions. Cancer Immunol Immunother 56(2):227–236PubMedCrossRefGoogle Scholar
  13. 13.
    Bodmer WF (1987) The HLA system: structure and function. J Clin Pathol 40:948–958PubMedCrossRefGoogle Scholar
  14. 14.
    Seliger B (2008) Different regulation of MHC class I antigen processing components in human tumors. J Immunotoxicol 5:361–367PubMedCrossRefGoogle Scholar
  15. 15.
    Campoli M, Ferrone S (2008) HLA antigen changes in malignant cells: epigenetic mechanisms and biologic significance. Oncogene 27:5869–5885PubMedCrossRefGoogle Scholar
  16. 16.
    Ruiz-Cabello F, Nevot MA, Garrido F (1988) MHC class I and II gene expression on human tumors. Adv Exp Med Biol 233:119–128PubMedGoogle Scholar
  17. 17.
    Seliger B, Stoehr R, Handke D, Mueller A, Ferrone S, Wullich B, Tannapfel A, Hofstaedter F, Hartmann A (2009) Association of HLA class I antigen abnormalities with disease progression and early recurrence in prostate cancer. Cancer Immunol Immunother 59:529–540PubMedCrossRefGoogle Scholar
  18. 18.
    Norell H, Carlsten M, Ohlum T, Malmberg KJ, Masucci G, Schedvins K, Altermann W, Handke D, Atkins D, Seliger B, Kiessling R (2006) Frequent loss of HLA-A2 expression in metastasizing ovarian carcinomas associated with genomic haplotype loss and HLA-A2-restricted HER-2/neu-specific immunity. Cancer Res 66:6387–6394PubMedCrossRefGoogle Scholar
  19. 19.
    Ljunggren HG, Malmberg KJ (2007) Prospects for the use of NK cells in immunotherapy of human cancer. Nat Rev Immunol 7:329–339PubMedCrossRefGoogle Scholar
  20. 20.
    Chan CJ, Andrews DM, Smyth MJ (2008) Can NK cells be a therapeutic target in human cancer? Eur J Immunol 38:2964–2968PubMedCrossRefGoogle Scholar
  21. 21.
    Hallett WH, Ames E, Motarjemi M, Barao I, Shanker A, Tamang DL, Sayers TJ, Hudig D, Murphy WJ (2008) Sensitization of tumor cells to NK cell-mediated killing by proteasome inhibition. J Immunol 180:163–170PubMedGoogle Scholar
  22. 22.
    Kruschinski A, Moosmann A, Poschke I, Norell H, Chmielewski M, Seliger B, Kiessling R, Blankenstein T, Abken H, Charo J (2008) Engineering antigen-specific primary human NK cells against HER-2 positive carcinomas. Proc Natl Acad Sci U S A 105:17481–17486PubMedCrossRefGoogle Scholar
  23. 23.
    Norell H, Poschke I, Charo J, Wei WZ, Erskine C, Piechocki MP, Knutson KL, Bergh J, Lidbrink E, Kiessling R (2010) Vaccination with a plasmid DNA encoding HER-2/neu together with low doses of GM-CSF and IL-2 in patients with metastatic breast carcinoma: a pilot clinical trial. J Transl Med 8:53PubMedCrossRefGoogle Scholar
  24. 24.
    Triulzi C, Vertuani S, Curcio C, Antognoli A, Seibt J, Akusjarvi G, Wei WZ, Cavallo F, Kiessling R (2010) Antibody-dependent natural killer cell-mediated cytotoxicity engendered by a kinase-inactive human HER2 adenovirus-based vaccination mediates resistance to breast tumors. Cancer Res 70:7431–7441PubMedCrossRefGoogle Scholar
  25. 25.
    Cozar JM, Canton J, Tallada M, Concha A, Cabrera T, Garrido F, Ruiz-Cabello Osuna F (2005) Analysis of NK cells and chemokine receptors in tumor infiltrating CD4 T lymphocytes in human renal carcinomas. Cancer Immunol Immunother 54:858–866PubMedCrossRefGoogle Scholar
  26. 26.
    Meyerhuber P, Conrad H, Starck L, Leisegang M, Busch DH, Uckert W, Bernhard H (2010) Targeting the epidermal growth factor receptor (HER) family by T cell receptor gene-modified T lymphocytes. J Mol Med 88:1113–1121PubMedCrossRefGoogle Scholar
  27. 27.
    Kraman M, Bambrough PJ, Arnold JN, Roberts EW, Magiera L, Jones JO, Gopinathan A, Tuveson DA, Fearon DT (2010) Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-alpha. Science 330:827–830PubMedCrossRefGoogle Scholar
  28. 28.
    Magner WJ, Kazim AL, Stewart C, Romano MA, Catalano G, Grande C, Keiser N, Santaniello F, Tomasi TB (2000) Activation of MHC class I, II, and CD40 gene expression by histone deacetylase inhibitors. J Immunol 165:7017–7024PubMedGoogle Scholar
  29. 29.
    Khan AN, Gregorie CJ, Tomasi TB (2008) Histone deacetylase inhibitors induce TAP, LMP, Tapasin genes and MHC class I antigen presentation by melanoma cells. Cancer Immunol Immunother 57:647–654PubMedCrossRefGoogle Scholar
  30. 30.
    Garrido C, Algarra I, Maleno I, Stefanski J, Collado A, Garrido F, Garcia-Lora AM (2009) Alterations of HLA class I expression in human melanoma xenografts in immunodeficient mice occur frequently and are associated with higher tumorigenicity. Cancer Immunol Immunother 59:13–26PubMedCrossRefGoogle Scholar
  31. 31.
    Fratta E, Sigalotti L, Colizzi F, Covre A, Nicolay HJ, Danielli R, Fonsatti E, Altomonte M, Calabro L, Coral S, Maio M (2010) Epigenetically regulated clonal heritability of CTA expression profiles in human melanoma. J Cell Physiol 223:352–358PubMedGoogle Scholar
  32. 32.
    Marks PA, Xu WS (2009) Histone deacetylase inhibitors: potential in cancer therapy. J Cell Biochem 107:600–608PubMedCrossRefGoogle Scholar
  33. 33.
    Bhat SA, Czuczman (2009) Novel antibodies in the treatment of non-Hodgkin’s lymphoma. Neth J Med 67:311–321PubMedGoogle Scholar
  34. 34.
    Huot R, Levy R (2009) Idiotype vaccination for lymphoma: moving towards optimisation. Leuk Lymphoma 50:1–2CrossRefGoogle Scholar
  35. 35.
    Timmerman JM, Vose JM, Czerwinski DK, Weng WK, Ingolia D, Mayo M, Denney DW, Levy R (2009) Tumor-specific recombinant idiotype immunisation after chemotherapy as initial treatment for follicular non-Hodgkin lymphoma. Leuk Lymphoma 50:37–46PubMedCrossRefGoogle Scholar
  36. 36.
    Chen CG, Lu YT, Lin M, Savelyeva N, Stevenson FK, Zhu D (2009) Amplification of immune responses against a DNA-delivered idiotypic lymphoma antigen by fusion to the B subunit of E. coli heat labile toxin. Vaccine 27:4289–4296PubMedCrossRefGoogle Scholar
  37. 37.
    Varghese B, Widman A, Do J, Taidi B, Czerwinski DK, Timmerman J, Levy S, Levy R (2009) Generation of CD8 + T cell-mediated immunity against idiotype-negative lymphoma escapees. Blood 114:4477–4485PubMedCrossRefGoogle Scholar
  38. 38.
    Wierda WG, Kipps TJ, Mayer J, Stilgenbauer S, Williams CD, Hellmann A, Robak T, Furman RR, Hillmen P, Trneny M, Dyer MJ, Padmanabhan S, Piotrowska M, Kozak T, Chan G, Davis R, Losic N, Wilms J, Russell CA, Osterborg A (2010) Ofatumumab as single-agent CD20 immunotherapy in fludarabine-refractory chronic lymphocytic leukemia. J Clin Oncol 28:1749–1755PubMedCrossRefGoogle Scholar
  39. 39.
    Flowers CR, Armitage JO (2010) A decade of progress in lymphoma: advances and continuing challenges. Clin Lymphoma Myeloma Leuk 10:414–423PubMedCrossRefGoogle Scholar
  40. 40.
    Keating GM (2010) Rituximab: a review of its use in chronic lymphocytic leukaemia, low-grade or follicular lymphoma and diffuse large B-cell lymphoma. Drugs 70:1445–1476PubMedCrossRefGoogle Scholar
  41. 41.
    Schaniel C, Gottar M, Roosnek E, Melchers F, Rolink AG (2002) Extensive in vivo self-renewal, long-term reconstitution capacity, and hematopoietic multipotency of Pax5-deficient precursor B-cell clones. Blood 99(8):2760–2766PubMedCrossRefGoogle Scholar
  42. 42.
    Ikawa T, Hirose S, Masuda K, Kakugawa K, Satoh R, Shibano-Satoh A, Kominami R, Katsura Y, Kawamoto H (2010) An essential developmental checkpoint for production of the T cell lineage. Science 329:93–96PubMedCrossRefGoogle Scholar
  43. 43.
    Kruser TJ, Wheeler DL (2010) Mechanisms of resistance to HER family targeting antibodies. Exp Cell Res 316:3639–3647CrossRefGoogle Scholar
  44. 44.
    Leth-Larsen R, Lund RR, Ditzel HJ (2010) Plasma membrane proteomics and its application in clinical cancer biomarker discovery. Mol Cell Proteomics 12:1369–1382Google Scholar
  45. 45.
    Hasegawa S, Furukawa Y, Li M, Satoh S, Kato T, Watanabe T, Katagiri T, Tsunoda T, Yamaoka Y, Nakamura Y (2002) Genome-wide analysis of gene expression in intestinal-type gastric cancers using a complementary DNA microarray representing 23, 040 genes. Cancer Res 62:7012–7017PubMedGoogle Scholar
  46. 46.
    Esseghir S, Reis-Filho JS, Kennedy A, James M, O’Hare MJ, Jeffery R, Poulsom R, Isacke CM (2006) Identification of transmembrane proteins as potential prognostic markers and therapeutic targets in breast cancer by a screen for signal sequence encoding transcripts. J Pathol 210:420–430PubMedCrossRefGoogle Scholar
  47. 47.
    Alsoe L, Stacy JE, Fossa A, Funderud S, Brekke OH, Gaudernack G (2008) Identification of prostate cancer antigens by automated high-throughput filter immunoscreening. J Immunol Methods 330:12–23PubMedCrossRefGoogle Scholar
  48. 48.
    Nelson AL, Dhimolea E, Reichert JM (2010) Development trends for human monoclonal antibody therapeutics. Nat Rev Drug Discov 9:767–774PubMedCrossRefGoogle Scholar
  49. 49.
    Chiang CL, Ledermann JA, Aitkens E, Benjamin E, Katz DR, Chain BM (2008) Oxidation of ovarian epithelial cancer cells by hypochlorous acid enhances immunogenicity and stimulates T cells that recognize autologous primary tumor. Clin Cancer Res 14:4898–4907PubMedCrossRefGoogle Scholar
  50. 50.
    Disis ML, Wallace DR, Gooley TA, Dang Y, Slota M, Lu H, Coveler AL, Childs JS, Higgins DM, Fintak PA, dela Rosa C, Tietje K, Link J, Waisman J, Salazar LG (2009) Concurrent trastuzumab and HER2/neu-specific vaccination in patients with metastatic breast cancer. J Clin Oncol 27:4685–4692PubMedCrossRefGoogle Scholar
  51. 51.
    Bhat R, Dempe S, Dinsart C, Rommelaere J (2011) Enhancement of NK cell anti-tumour responses using an oncolytic parvovirus. Int J Cancer 128:908–919PubMedCrossRefGoogle Scholar
  52. 52.
    Pandha H, Melcher A, Harrington K, Vile R (2009) Oncolytic viruses: time to compare, contrast, and combine? Mol Ther 17:934–935PubMedCrossRefGoogle Scholar
  53. 53.
    Natsume A, Kondo Y, Ito M, Motomura K, Wakabayashi T, Yoshida J (2010) Epigenetic aberrations and therapeutic implications in gliomas. Cancer Sci 101:1331–1336PubMedCrossRefGoogle Scholar
  54. 54.
    Dhodapkar MV (2010) Immunity to stemness genes in human cancer. Curr Opin Immunol 22:245–250PubMedCrossRefGoogle Scholar
  55. 55.
    Moore N, Lyle S (2010) Quiescent, slow-cycling stem cell populations in cancer: a review of the evidence and discussion of significance. J Oncol 2011–2022Google Scholar
  56. 56.
    Jin L, Lee EM, Ramshaw HS, Busfield SJ, Peoppl AG, Wilkinson L, Guthridge MA, Thomas D, Barry EF, Boyd A, Gearing DP, Vairo G, Lopez AF, Dick JE, Lock RB (2009) Monoclonal antibody-mediated targeting of CD123, IL-3 receptor alpha chain, eliminates human acute myeloid leukemic stem cells. Cell Stem Cell 5:31–42PubMedCrossRefGoogle Scholar
  57. 57.
    Agarwala SS, Case S (2010) Everolimus (RAD001) in the treatment of advanced renal cell carcinoma: a review. Oncologist 15:236–245PubMedCrossRefGoogle Scholar
  58. 58.
    Romero P, Cerottini JC, Speiser DE (2006) The human T cell response to melanoma antigens. Adv Immunol 92:187–224PubMedCrossRefGoogle Scholar
  59. 59.
    Caballero OL, Zhao Q, Rimoldi D, Stevenson BJ, Svobodova S, Devalle S, Rohrig UF, Pagotto A, Michielin O, Speiser D, Wolchok JD, Liu C, Pejovic T, Odunsi K, Brasseur F, Van den Eynde BJ, Old LJ, Lu X, Cebon J, Strausberg RL, Simpson AJ (2010) Frequent MAGE mutations in human melanoma. PLoS One 5Google Scholar
  60. 60.
    Beverley PC, Lowenthal RM, Tyrrell DA (1973) Immune responses in mice to tumour challenge after immunization with Newcastle disease virus-infected or x-irradiated tumour cells or cell fractions. Int J Cancer 11:212–223PubMedCrossRefGoogle Scholar
  61. 61.
    Peggs KS, Quezada SA, Korman AJ, Allison JP (2006) Principles and use of anti-CTLA4 antibody in human cancer immunotherapy. Curr Opin Immunol 18:206–213PubMedCrossRefGoogle Scholar
  62. 62.
    Yamaguchi T, Sakaguchi S (2006) Regulatory T cells in immune surveillance and treatment of cancer. Semin Cancer Biol 16:115–123PubMedCrossRefGoogle Scholar
  63. 63.
    Kortylewski M, Swiderski P, Herrmann A, Wang L, Kowolik C, Kujawski M, Lee H, Scuto A, Liu Y, Yang C, Deng J, Soifer HS, Raubitschek A, Forman S, Rossi JJ, Pardoll DM, Jove R, Yu H (2009) In vivo delivery of siRNA to immune cells by conjugation to a TLR9 agonist enhances antitumor immune responses. Nat Biotechnol 27:925–932PubMedCrossRefGoogle Scholar
  64. 64.
    Groh V, Li YQ, Cioca D, Hunder NN, Wang W, Riddell SR, Yee C, Spies T (2005) Efficient cross-priming of tumor antigen-specific T cells by dendritic cells sensitized with diverse anti-MICA opsonized tumor cells. Proc Natl Acad Sci U S A 102:6461–6466PubMedCrossRefGoogle Scholar
  65. 65.
    Sancho D, Mourao-Sa D, Joffre OP, Schulz O, Rogers NC, Pennington DJ, Carlyle JR, Reis e Sousa C (2008) Tumor therapy in mice via antigen targeting to a novel, DC-restricted C-type lectin. J Clin Invest 118:2098PubMedCrossRefGoogle Scholar
  66. 66.
    Arce F, Rowe HM, Chain B, Lopes L, Collins MK (2009) Lentiviral vectors transduce proliferating dendritic cell precursors leading to persistent antigen presentation and immunization. Mol Ther 17:1643–1650PubMedCrossRefGoogle Scholar
  67. 67.
    Xue SA, Gao L, Thomas S, Hart DP, Xue JZ, Gillmore R, Voss RH, Morris E, Stauss HJ (2009) Development of a Wilms’ tumor antigen-specific T-cell receptor for clinical trials: engineered patient’s T cells can eliminate autologous leukemia blasts in NOD/SCID mice. Haematologica 95:126–134PubMedCrossRefGoogle Scholar
  68. 68.
    Stevenson FK, Ottensmeier CH, Rice J (2010) DNA vaccines against cancer come of age. Curr Opin Immunol 22:264–270PubMedCrossRefGoogle Scholar
  69. 69.
    Theurillat JP, Ingold F, Frei C, Zippelius A, Varga Z, Seifert B, Chen YT, Jager D, Knuth A, Moch H (2007) NY-ESO-1 protein expression in primary breast carcinoma and metastases: correlation with CD8 + T-cell and CD79a + plasmacytic/B-cell infiltration. Int J Cancer 120:2411–2417PubMedCrossRefGoogle Scholar
  70. 70.
    Knights AJ, Nuber N, Thomson CW, de la Rosa O, Jager E, Tiercy JM, van den Broek M, Pascolo S, Knuth A, Zippelius A (2009) Modified tumour antigen-encoding mRNA facilitates the analysis of naturally occurring and vaccine-induced CD4 and CD8 T cells in cancer patients. Cancer Immunol Immunother 58:325–338PubMedCrossRefGoogle Scholar
  71. 71.
    Kim PS, Armstrong TD, Song H, Wolpoe ME, Weiss V, Manning EA, Huang LQ, Murata S, Sgouros G, Emens LA, Reilly RT, Jaffee EM (2008) Antibody association with HER-2/neu-targeted vaccine enhances CD8 T cell responses in mice through Fc-mediated activation of DCs. J Clin Invest 118:1700–1711PubMedCrossRefGoogle Scholar
  72. 72.
    Topalian SL, Rosenberg SA (1987) Therapy of cancer using the adoptive transfer of activated killer cells and interleukin-2. Acta Haematol 78(Suppl 1):75–76Google Scholar
  73. 73.
    Dudley ME, Rosenberg SA (2003) Adoptive-cell-transfer therapy for the treatment of patients with cancer. Nat Rev Cancer 3:666–675PubMedCrossRefGoogle Scholar
  74. 74.
    Morgan RA, Dudley ME, Rosenberg SA (2010) Adoptive cell therapy: genetic modification to redirect effector cell specificity. Cancer J 16:336–341PubMedCrossRefGoogle Scholar
  75. 75.
    Frankenberger B, Regn S, Geiger C, Noessner E, Falk CS, Pohla H, Javorovic M, Silberzahn T, Wilde S, Buchner A, Siebels M, Oberneder R, Willimsky G, Pezzutto A, Blankenstein T, Schendel DJ (2005) Cell-based vaccines for renal cell carcinoma: genetically-engineered tumor cells and monocyte-derived dendritic cells. World J Urol 23:166–174PubMedCrossRefGoogle Scholar
  76. 76.
    Schendel DJ (2007) Dendritic cell vaccine strategies for renal cell carcinoma. Expert Opin Biol Ther 7:221–232PubMedCrossRefGoogle Scholar
  77. 77.
    Spranger S, Javorovic M, Burdek M, Wilde S, Mosetter B, Tippmer S, Bigalke I, Geiger C, Schendel DJ, Frankenberger B (2010) Generation of Th1-polarizing dendritic cells using the TLR7/8 agonist CL075. J Immunol 185:738–747PubMedCrossRefGoogle Scholar
  78. 78.
    Buchner A, Pohla H, Willimsky G, Frankenberger B, Frank R, Baur-Melnyk A, Siebels M, Stief CG, Hofstetter A, Kopp J, Pezzutto A, Blankenstein T, Oberneder R, Schendel DJ (2010) Phase 1 trial of allogeneic gene-modified tumor cell vaccine RCC-26/CD80/IL-2 in patients with metastatic renal cell carcinoma. Hum Gene Ther 21:285–297PubMedCrossRefGoogle Scholar
  79. 79.
    Palmer DC, Chan CC, Gattinoni L, Wrzesinski C, Paulos CM, Hinrichs CS, Powell DJ Jr, Klebanoff CA, Finkelstein SE, Fariss RN, Yu Z, Nussenblatt RB, Rosenberg SA, Restifo NP (2008) Effective tumor treatment targeting a melanoma/melanocyte-associated antigen triggers severe ocular autoimmunity. Proc Natl Acad Sci U S A 105:8061–8066PubMedCrossRefGoogle Scholar
  80. 80.
    Klebanoff CA, Yu Z, Hwang LN, Palmer DC, Gattinoni L, Restifo NP (2009) Programming tumor-reactive effector memory CD8 + T cells in vitro obviates the requirement for in vivo vaccination. Blood 114:1776–1783. doi:10.1182/blood-2008-12-192419 PubMedCrossRefGoogle Scholar
  81. 81.
    Lu C, Williams AK, Chalasani V, Martinez CH, Chin J (2010) Immunotherapy for metastatic prostate cancer: where are we at with sipuleucel-T? Expert Opin Biol Ther 11:99–108. 82Google Scholar
  82. 82.
    Ruttinger D, Winter H, van den Engel NK, Hatz R, Jauch KW, Fox BA, Weber JS (2010) Immunotherapy of cancer: key findings and commentary on the third Tegernsee conference. Oncologist 15:112–118PubMedCrossRefGoogle Scholar
  83. 83.
    Hamid O, Solomon JC, Scotland R, Garcia M, Sian S, Ye W, Groshen SL, Weber JS (2007) Alum with interleukin-12 augments immunity to a melanoma peptide vaccine: correlation with time to relapse in patients with resected high-risk disease. Clin Cancer Res 13:215–222PubMedCrossRefGoogle Scholar
  84. 84.
    O’Day SJ, Atkins MB, Boasberg P, Wang HJ, Thompson JA, Anderson CM, Gonzalez R, Lutzky J, Amatruda T, Hersh EM, Weber JS (2009) Phase II multicenter trial of maintenance biotherapy after induction concurrent biochemotherapy for patients with metastatic melanoma. J Clin Oncol 27:6207–6212PubMedCrossRefGoogle Scholar
  85. 85.
    Hersh EM, O’Day SJ, Powderly J, Khan KD, Pavlick AC, Cranmer LD, Samlowski WE, Nichol GM, Yellin MJ, Weber JS (2010) A phase II multicenter study of ipilimumab with or without dacarbazine in chemotherapy-naive patients with advanced melanoma. Invest New Drugs. Ref details not availableGoogle Scholar
  86. 86.
    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 363:711–723PubMedCrossRefGoogle Scholar
  87. 87.
    Ribas A, Comin-Anduix B, Chmielowski B, Jalil J, de la Rocha P, McCannel TA, Ochoa MT, Seja E, Villanueva A, Oseguera DK, Straatsma BR, Cochran AJ, Glaspy JA, Hui L, Marincola FM, Wang E, Economou JS, Gomez-Navarro J (2009) Dendritic cell vaccination combined with CTLA4 blockade in patients with metastatic melanoma. Clin Cancer Res 15:6267–6276PubMedCrossRefGoogle Scholar
  88. 88.
    von Euw E, Chodon T, Attar N, Jalil J, Koya RC, Comin-Anduix B, Ribas A (2009) CTLA4 blockade increases Th17 cells in patients with metastatic melanoma. J Transl Med 7:35CrossRefGoogle Scholar
  89. 89.
    Cohen AD, Schaer DA, Liu C, Li Y, Hirschhorn-Cymmerman D, Kim SC, Diab A, Rizzuto G, Duan F, Perales MA, Merghoub T, Houghton AN, Wolchok JD (2010) Agonist anti-GITR monoclonal antibody induces melanoma tumor immunity in mice by altering regulatory T cell stability and intra-tumor accumulation. PLoS One 5:e10436PubMedCrossRefGoogle Scholar
  90. 90.
    Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, Stankevich E, Pons A, Salay TM, McMiller TL, Gilson MM, Wang C, Selby M, Taube JM, Anders R, Chen L, Korman AJ, Pardoll DM, Lowy I, Topalian SL (2010) Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol 28:3167–3175PubMedCrossRefGoogle Scholar
  91. 91.
    Wang W, Lau R, Yu D, Zhu W, Korman A, Weber J (2009) PD1 blockade reverses the suppression of melanoma antigen-specific CTL by CD4 + CD25(Hi) regulatory T cells. Int Immunol 21:1065–1077PubMedCrossRefGoogle Scholar
  92. 92.
    Breckpot K, Heirman C, De Greef C, van der Bruggen P, Thielemans K (2004) Identification of new antigenic peptide presented by HLA-Cw7 and encoded by several MAGE genes using dendritic cells transduced with lentiviruses. J Immunol 172:2232–2237PubMedGoogle Scholar
  93. 93.
    Maslak PG, Dao T, Krug LM, Chanel S, Korontsvit T, Zakhaleva V, Zhang R, Wolchok JD, Yuan J, Pinilla-Ibarz J, Berman E, Weiss M, Jurcic J, Frattini MG, Scheinberg DA (2010) Vaccination with synthetic analog peptides derived from WT1 oncoprotein induces T-cell responses in patients with complete remission from acute myeloid leukemia. Blood 116:171–179PubMedCrossRefGoogle Scholar
  94. 94.
    Weden S, Klemp M, Gladhaug IP, Moller M, Eriksen JA, Gaudernack G, Buanes T (2010) Long-term follow-up of patients with resected pancreatic cancer following vaccination against mutant K-ras. Int J Cancer 128:1120–1128CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Yeranddy A. Alpizar
    • 1
  • Benjamin Chain
    • 2
  • Mary K. Collins
    • 2
  • John Greenwood
    • 3
  • David Katz
    • 2
  • Hans J. Stauss
    • 3
  • N. Avrion Mitchison
    • 3
  1. 1.Division of Tumoral BiologyCentre for Molecular ImmunologyHabanaCuba
  2. 2.Division of Infection and ImmunityUniversity College London (UCL)LondonUK
  3. 3.UCL Institute of OphthalmologyLondonUK

Personalised recommendations