Interleukin-21 and Cancer Therapy

  • Ian D. Davis
  • Kresten Skak
  • Naomi Hunder
  • Mark J. Smyth
  • Pallavur V. Sivakumar


Interleukin-21 (IL-21) is a pleiotropic cytokine structurally similar to IL-2 and IL-15 but with important distinctions in its biological properties. IL-21 is mainly secreted by activated CD4+ T cells, NKT cells, and follicular T helper (Tfh) cells. The IL-21 receptor is expressed physiologically on lymphoid tissues and peripheral blood mononuclear cells, although expression can be acquired by epithelial, synovial, or transformed cells. The effects of IL-21 signaling include enhancement of adaptive T cell immunity, promotion of antibody production, activation of innate immune responses through NK cells, opposition to immune downmodulation mediated through regulatory T cells, and effects in autoimmunity. IL-21 also has important roles in development of Th17 and Tfh cells. In preclinical models and clinical trials in humans, IL-21 has been shown to mediate anticancer effects either as a single agent or in combination with other strategies such as monoclonal antibodies or tyrosine kinase inhibitors. The biology of IL-21 suggests that it could also be usefully combined with active vaccination, adoptive immunotherapy, or cytotoxic chemotherapy. IL-21 continues to undergo clinical development for a variety of cancer indications.


Renal Cell Carcinoma Antitumor Effect Capillary Leak Syndrome Adoptive Cell Therapy Preclinical Tumor Model 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



IDD is supported in part by a Victorian Cancer Agency Clinician Researcher Fellowship and is an Australian National Health and Medical Research Council Honorary Practitioner Fellow. MJS is supported by a NH&MRC Senior Principal Research Fellowship and Program Grant.


  1. 1.
    Bondensgaard, K., Breinholt, J., Madsen, D., Omkvist, D. H., Kang, L., Worsaae, A., Becker, P., Schiodt, C. B., and Hjorth, S. A. (2007) J Biol Chem 282, 23326PubMedGoogle Scholar
  2. 2.
    Asao, H., Okuyama, C., Kumaki, S., Ishii, N., Tsuchiya, S., Foster, D., and Sugamura, K. (2001) J Immunol 167, 1PubMedGoogle Scholar
  3. 3.
    Habib, T., Senadheera, S., Weinberg, K., and Kaushansky, K. (2002) Biochemistry 41, 8725PubMedGoogle Scholar
  4. 4.
    Brenne, A. T., Ro, T. B., Waage, A., Sundan, A., Borset, M., and Hjorth-Hansen, H. (2002) Blood 99, 3756PubMedGoogle Scholar
  5. 5.
    Strengell, M., Matikainen, S., Siren, J., Lehtonen, A., Foster, D., Julkunen, I., and Sareneva, T. (2003) J Immunol 170, 5464PubMedGoogle Scholar
  6. 6.
    Zeng, R., Spolski, R., Casas, E., Zhu, W., Levy, D. E., and Leonard, W. J. (2007) Blood 109, 4135PubMedGoogle Scholar
  7. 7.
    Jin, H., Carrio, R., Yu, A., and Malek, T. R. (2004) J Immunol 173, 657PubMedGoogle Scholar
  8. 8.
    Parrish-Novak, J., Dillon, S. R., Nelson, A., Hammond, A., Sprecher, C., Gross, J. A., Johnston, J., Madden, K., Xu, W., West, J., Schrader, S., Burkhead, S., Heipel, M., Brandt, C., Kuijper, J. L., Kramer, J., Conklin, D., Presnell, S. R., Berry, J., Shiota, F., Bort, S., Hambly, K., Mudri, S., Clegg, C., Moore, M., Grant, F. J., Lofton-Day, C., Gilbert, T., Rayond, F., Ching, A., Yao, L., Smith, D., Webster, P., Whitmore, T., Maurer, M., Kaushansky, K., Holly, R. D., and Foster, D. (2000) Nature 408, 57PubMedGoogle Scholar
  9. 9.
    Distler, J. H., Jüngel, A., Kowal-Bielecka, O., Michel, B. A., Gay, R. E., Sprott, H., Matucci-Cerinic, M., Chilla, M., Reich, K., Kalden, J. R., Muller-Ladner, U., Lorenz, H. M., Gay, S., and Distler, O. (2005) Arthritis Rheum 52, 856PubMedGoogle Scholar
  10. 10.
    Jüngel, A., Distler, J. H., Kurowska-Stolarska, M., Seemayer, C. A., Seibl, R., Forster, A., Michel, B. A., Gay, R. E., Emmrich, F., Gay, S., and Distler, O. (2004) Arthritis Rheum 50, 1468PubMedGoogle Scholar
  11. 11.
    Monteleone, G., Caruso, R., Fina, D., Peluso, I., Gioia, V., Stolfi, C., Fantini, M. C., Caprioli, F., Tersigni, R., Alessandroni, L., MacDonald, T. T., and Pallone, F. (2006) Gut 55, 1774PubMedGoogle Scholar
  12. 12.
    Coquet, J. M., Kyparissoudis, K., Pellicci, D. G., Besra, G., Berzins, S. P., Smyth, M. J., and Godfrey, D. I. (2007) J Immunol 178, 2827PubMedGoogle Scholar
  13. 13.
    Suto, A., Kashiwakuma, D., Kagami, S., Hirose, K., Watanabe, N., Yokote, K., Saito, Y., Nakayama, T., Grusby, M. J., Iwamoto, I., and Nakajima, H. (2008) J Exp Med 205, 1369PubMedGoogle Scholar
  14. 14.
    Dunn, G. P., Bruce, A. T., Ikeda, H., Old, L. J., and Schreiber, R. D. (2002) Nat Immunol 3, 991PubMedGoogle Scholar
  15. 15.
    Ozaki, K., Spolski, R., Feng, C. G., Qi, C.-F., Cheng, J., Sher, A., Morse, H. C., III, Liu, C., Schwartzberg, P. L., and Leonard, W. J. (2002) Science 298, 1630PubMedGoogle Scholar
  16. 16.
    Wurster, A. L., Rodgers, V. L., Satoskar, A. R., Whitters, M. J., Young, D. A., Collins, M., and Grusby, M. J. (2002) J Exp Med 196, 969PubMedGoogle Scholar
  17. 17.
    Strengell, M., Sareneva, T., Foster, D., Julkunen, I., and Matikainen, S. (2002) J Immunol 169, 3600PubMedGoogle Scholar
  18. 18.
    Pesce, J., Kaviratne, M., Ramalingam, T. R., Thompson, R. W., Urban, J. F., Cheever, A. W., Young, D. A., Collins, M., Grusby, M. J., and Wynn, T. A. (2006) J Clin Invest 116, 2044PubMedGoogle Scholar
  19. 19.
    Frohlich, A., Marsland, B. J., Sonderegger, I., Kurrer, M., Hodge, M. R., Harris, N. L., and Kopf, M. (2007) Blood 109, 2023PubMedGoogle Scholar
  20. 20.
    Korn, T., Bettelli, E., Gao, W., Awasthi, A., Jager, A., Strom, T. B., Oukka, M., and Kuchroo, V. K. (2007) Nature 448, 484PubMedGoogle Scholar
  21. 21.
    Nurieva, R., Yang, X. O., Martinez, G., Zhang, Y., Panopoulos, A. D., Ma, L., Schluns, K., Tian, Q., Watowich, S. S., Jetten, A. M., and Dong, C. (2007) Nature 448, 480PubMedGoogle Scholar
  22. 22.
    Zhou, L., Ivanov, I., Spolski, R., Min, R., Shenderov, K., Egawa, T., Levy, D. E., Leonard, W. J., and Littman, D. R. (2007) Nat Immunol 8, 967PubMedGoogle Scholar
  23. 23.
    Coquet, J. M., Chakravarti, S., Smyth, M. J., and Godfrey, D. I. (2008) J Immunol 180, 7097PubMedGoogle Scholar
  24. 24.
    Yang, L., Anderson, D. E., Baecher-Allan, C., Hastings, W. D., Bettelli, E., Oukka, M., Kuchroo, V. K., and Hafler, D. A. (2008) Nature 454, 350PubMedGoogle Scholar
  25. 25.
    Sonderegger, I., Kisielow, J., Meier, R., King, C., and Kopf, M. (2008) Eur J Immunol 38, 1833PubMedGoogle Scholar
  26. 26.
    Chtanova, T., Tangye, S. G., Newton, R., Frank, N., Hodge, M. R., Rolph, M. S., and Mackay, C. R. (2004) J Immunol 173, 68PubMedGoogle Scholar
  27. 27.
    Vogelzang, A., McGuire, H. M., Yu, D., Sprent, J., Mackay, C. R., and King, C. (2008) Immunity 29, 127PubMedGoogle Scholar
  28. 28.
    Nurieva, R. I., Chung, Y., Hwang, D., Yang, X. O., Kang, H. S., Ma, L., Wang, Y. H., Watowich, S. S., Jetten, A. M., Tian, Q., and Dong, C. (2008) Immunity 29, 138PubMedGoogle Scholar
  29. 29.
    Zeng, R., Spolski, R., Finkelstein, S. E., Oh, S., Kovanen, P. E., Hinrichs, C. S., Pise-Masison, C. A., Radonovich, M. F., Brady, J. N., Restifo, N. P., Berzofsky, J. A., and Leonard, W. J. (2005) J Exp Med 201, 139PubMedGoogle Scholar
  30. 30.
    Alves, N. L., Arosa, F. A., and van Lier, R. A. (2005) J Immunol 175, 755PubMedGoogle Scholar
  31. 31.
    Li, Y., Bleakley, M., and Yee, C. (2005) J Immunol 175, 2261PubMedGoogle Scholar
  32. 32.
    White, L., Krishnan, S., Strbo, N., Liu, H., Kolber, M. A., Lichtenheld, M. G., Pahwa, R., and Pahwa, S. (2007) Blood 109, 3873PubMedGoogle Scholar
  33. 33.
    Hinrichs, C. S., Spolski, R., Paulos, C. M., Gattinoni, L., Kerstann, K. W., Palmer, D. C., Klebanoff, C. A., Rosenberg, S. A., Leonard, W. J., and Restifo, N. P. (2008) Blood 111, 5326PubMedGoogle Scholar
  34. 34.
    Shevach, E. M. (2006) Immunity 25, 195PubMedGoogle Scholar
  35. 35.
    Fantini, M. C., Rizzo, A., Fina, D., Caruso, R., Becker, C., Neurath, M. F., MacDonald, T. T., Pallone, F., and Monteleone, G. (2007) Eur J Immunol 37, 3155PubMedGoogle Scholar
  36. 36.
    Peluso, I., Fantini, M. C., Fina, D., Caruso, R., Boirivant, M., MacDonald, T. T., Pallone, F., and Monteleone, G. (2007) J Immunol 178, 732PubMedGoogle Scholar
  37. 37.
    Antony, P. A., and Restifo, N. P. (2005) J Immunother 28, 120PubMedGoogle Scholar
  38. 38.
    Ahmadzadeh, M., Antony, P. A., and Rosenberg, S. A. (2007) J Immunother 30, 294PubMedGoogle Scholar
  39. 39.
    Kasaian, M. T., Whitters, M. J., Carter, L. L., Lowe, L. D., Jussif, J. M., Deng, B., Johnson, K. A., Witek, J. S., Senices, M., Konz, R. F., Wurster, A. L., Donaldson, D. D., Collins, M., Young, D. A., and Grusby, M. J. (2002) Immunity 16, 559PubMedGoogle Scholar
  40. 40.
    Brady, J., Hayakawa, Y., Smyth, M. J., and Nutt, S. L. (2004) J Immunol 172, 2048PubMedGoogle Scholar
  41. 41.
    Roda, J. M., Parihar, R., Lehman, A., Mani, A., Tridandapani, S., and Carson, W. E., III (2006) J Immunol 177, 120PubMedGoogle Scholar
  42. 42.
    Skak, K., Frederiksen, K. S., and Lundsgaard, D. (2008) Immunology 123, 575PubMedGoogle Scholar
  43. 43.
    Mehta, D. S., Wurster, A. L., Whitters, M. J., Young, D. A., Collins, M., and Grusby, M. J. (2003) J Immunol 170, 4111PubMedGoogle Scholar
  44. 44.
    Ozaki, K., Spolski, R., Ettinger, R., Kim, H. P., Wang, G., Qi, C. F., Hwu, P., Shaffer, D. J., Akilesh, S., Roopenian, D. C., Morse, H. C., III, Lipsky, P. E., and Leonard, W. J. (2004) J Immunol 173, 5361PubMedGoogle Scholar
  45. 45.
    Spolski, R., and Leonard, W. J. ( 2008) Annu Rev Immunol 26, 57PubMedGoogle Scholar
  46. 46.
    Wood, N., Bourque, K., Donaldson, D. D., Collins, M., Vercelli, D., Goldman, S. J., and Kasaian, M. T. (2004) Cell Immunol 231, 133PubMedGoogle Scholar
  47. 47.
    Ettinger, R., Sims, G. P., Fairhurst, A. M., Robbins, R., da Silva, Y. S., Spolski, R., Leonard, W. J., and Lipsky, P. E. (2005) J Immunol 175, 7867PubMedGoogle Scholar
  48. 48.
    Vinuesa, C. G., Cook, M. C., Angelucci, C., Athanasopoulos, V., Rui, L., Hill, K. M., Yu, D., Domaschenz, H., Whittle, B., Lambe, T., Roberts, I. S., Copley, R. R., Bell, J. I., Cornall, R. J., and Goodnow, C. C. (2005) Nature 435, 452PubMedGoogle Scholar
  49. 49.
    Herber, D., Brown, T. P., Liang, S., Young, D. A., Collins, M., and Dunussi-Joannopoulos, K. (2007) J Immunol 178, 3822PubMedGoogle Scholar
  50. 50.
    Young, D. A., Hegen, M., Ma, H. L., Whitters, M. J., Albert, L. M., Lowe, L., Senices, M., Wu, P. W., Sibley, B., Leathurby, Y., Brown, T. P., Nickerson-Nutter, C., Keith, J. C., Jr., and Collins, M. (2007) Arthritis Rheum 56, 1152PubMedGoogle Scholar
  51. 51.
    de Totero, D., Meazza, R., Zupo, S., Cutrona, G., Matis, S., Colombo, M., Balleari, E., Pierri, I., Fabbi, M., Capaia, M., Azzarone, B., Gobbi, M., Ferrarini, M., and Ferrini, S. (2006) Blood 107, 3708PubMedGoogle Scholar
  52. 52.
    Akamatsu, N., Yamada, Y., Hasegawa, H., Makabe, K., Asano, R., Kumagai, I., Murata, K., Imaizumi, Y., Tsukasaki, K., Tsuruda, K., Sugahara, K., Atogami, S., Yanagihara, K., and Kamihira, S. (2007) Cancer Lett 256, 196PubMedGoogle Scholar
  53. 53.
    de Totero, D., Meazza, R., Capaia, M., Fabbi, M., Azzarone, B., Balleari, E., Gobbi, M., Cutrona, G., Ferrarini, M., and Ferrini, S. (2008) Blood 111, 517PubMedGoogle Scholar
  54. 54.
    Gowda, A., Roda, J., Hussain, S. R., Ramanunni, A., Joshi, T., Schmidt, S., Zhang, X., Lehman, A., Jarjoura, D., Carson, W. E., Kindsvogel, W., Cheney, C., Caligiuri, M. A., Tridandapani, S., Muthusamy, N., and Byrd, J. C. (2008) Blood 111, 4723PubMedGoogle Scholar
  55. 55.
    Jahrsdorfer, B., Blackwell, S. E., Wooldridge, J. E., Huang, J., Andreski, M. W., Jacobus, L. S., Taylor, C. M., and Weiner, G. J. (2006) Blood 108, 2712PubMedGoogle Scholar
  56. 56.
    Bolesta, E., Kowalczyk, A., Wierzbicki, A., Eppolito, C., Kaneko, Y., Takiguchi, M., Stamatatos, L., Shrikant, P. A., and Kozbor, D. (2006) J Immunol 177, 177PubMedGoogle Scholar
  57. 57.
    Iuchi, T., Teitz-Tennenbaum, S., Huang, J., Redman, B. G., Hughes, S. D., Li, M., Jiang, G., Chang, A. E., and Li, Q. (2008) Cancer Res 68, 4431PubMedGoogle Scholar
  58. 58.
    Skak, K., Kragh, M., Hausman, D., Smyth, M. J., and Sivakumar, P. V. (2008) Nat Rev Drug Discov 7, 231PubMedGoogle Scholar
  59. 59.
    Søndergaard, H., Frederiksen, K. S., Thygesen, P., Galsgaard, E. D., Skak, K., Kristjansen, P. E., Odum, N., and Kragh, M. (2007) Cancer Immunol Immunother 56, 1417PubMedGoogle Scholar
  60. 60.
    Wang, G., Tschoi, M., Spolski, R., Lou, Y., Ozaki, K., Feng, C., Kim, G., Leonard, W. J., and Hwu, P. (2003) Cancer Res 63, 9016PubMedGoogle Scholar
  61. 61.
    Ma, H.-L., Whitters, M. J., Konz, R. F., Senices, M., Young, D. A., Grusby, M. J., Collins, M., and Dunussi-Joannopoulos, K. (2003) J Immunol 171, 608PubMedGoogle Scholar
  62. 62.
    Comes, A., Rosso, O., Orengo, A. M., Di Carlo, E., Sorrentino, C., Meazza, R., Piazza, T., Valzasina, B., Nanni, P., Colombo, M. P., and Ferrini, S. (2006) J Immunol 176, 1750PubMedGoogle Scholar
  63. 63.
    Furukawa, J., Hara, I., Nagai, H., Yao, A., Oniki, S., and Fujisawa, M. (2006) J Urol 176, 1198PubMedGoogle Scholar
  64. 64.
    Kumano, M., Hara, I., Furukawa, J., Oniki, S., Nagai, H., Miyake, H., and Fujisawa, M. (2007) J Urol 178, 1504PubMedGoogle Scholar
  65. 65.
    Daga, A., Orengo, A. M., Gangemi, R. M., Marubbi, D., Perera, M., Comes, A., Ferrini, S., and Corte, G. (2007) Int J Cancer 121, 1756PubMedGoogle Scholar
  66. 66.
    Ugai, S., Shimozato, O., Kawamura, K., Wang, Y. Q., Yamaguchi, T., Saisho, H., Sakiyama, S., and Tagawa, M. (2003) Cancer Gene Ther 10, 187PubMedGoogle Scholar
  67. 67.
    Croce, M., Meazza, R., Orengo, A. M., Fabbi, M., Borghi, M., Ribatti, D., Nico, B., Carlini, B., Pistoia, V., Corrias, M. V., and Ferrini, S. (2008) Cancer Immunol Immunother 57, 1625PubMedGoogle Scholar
  68. 68.
    Moroz, A., Eppolito, C., Li, Q., Tao, J., Clegg, C. H., and Shrikant, P. A. (2004) J Immunol 173, 900PubMedGoogle Scholar
  69. 69.
    Cvetkovic, R. S., and Perry, C. M. (2006) BioDrugs 20, 253PubMedGoogle Scholar
  70. 70.
    Dall’Ozzo, S., Tartas, S., Paintaud, G., Cartron, G., Colombat, P., Bardos, P., Watier, H., and Thibault, G. (2004) Cancer Res 64, 4664PubMedGoogle Scholar
  71. 71.
    Roda, J. M., Joshi, T., Butchar, J. P., McAlees, J. W., Lehman, A., Tridandapani, S., and Carson, W. E., III (2007) Clin Cancer Res 13, 6419PubMedGoogle Scholar
  72. 72.
    Smyth, M. J., Hayakawa, Y., Cretney, E., Zerafa, N., Sivakumar, P., Yagita, H., and Takeda, K. (2006) J Immunol 176, 6347PubMedGoogle Scholar
  73. 73.
    Smyth, M. J., Teng, M. W. L., Sharkey, J., Westwood, J. A., Haynes, N. M., Yagita, H., Takeda, K., Sivakumar, P. V., and Kershaw, M. H. (2008) Cancer Res 68, 3019PubMedGoogle Scholar
  74. 74.
    Davis, I. D., Skrumsager, B. K., Cebon, J., Nicholaou, T., Barlow, J. W., Moller, N. P. H., Skak, K., Lundsgaard, D., Frederiksen, K. S., Thygesen, P., and McArthur, G. A. (2007) Clin Cancer Res 13, 3630PubMedGoogle Scholar
  75. 75.
    Thompson, J. A., Curti, B. D., Redman, B. G., Bhatia, S., Weber, J. S., Agarwala, S. S., Sievers, E. L., Hughes, S. D., DeVries, T. A., and Hausman, D. F. (2008) J Clin Oncol 26, 2034PubMedGoogle Scholar
  76. 76.
    Frederiksen, K. S., Lundsgaard, D., Freeman, J. A., Hughes, S. D., Holm, T. L., Skrumsager, B. K., Petri, A., Hansen, L. T., McArthur, G. A., Davis, I. D., and Skak, K. (2008) Cancer Immunol Immunother 57, 1439PubMedGoogle Scholar
  77. 77.
    Davis, I. D., Brady, B., Kefford, R., Millward, M. J., Skrumsager, B. K., Mouritzen, U., Kristjansen, P. E., and McArthur, G. A. (2008) J Clin Oncol 26, 3042Google Scholar
  78. 77A.
    Davis, I. D., Brady, B., Kefford, R. F., Millward, M., Cebor, J., Skrumsager, B. K., Mouritzen, U., Hansen, L. T., Skak, K., Lundsgaard, D., Frederiksen, K. S., Kristjansen, P. E., McArthur, G. (2009) Clin Cancer Res 15, 2123PubMedGoogle Scholar
  79. 78.
    Timmerman, J. M., Byrd, J. C., Andorsky, D. J., Siadak, M. F., DeVries, T., Hausman, D. F., and Pagel, J. M. (2007) ASH Annual Meeting Abstracts 110: 2577Google Scholar
  80. 79.
    Timmerman, J. M., Byrd, J. C., Andorsky, D. J., Siadak, M. F., DeVries, T. A., Hausman, D. F., and Pagel, J. M. (2008) J Clin Oncol 26, 8554Google Scholar
  81. 80.
    Pezaro, C., and Davis, I. D. (2008) Curr Med Chem 15, 1166PubMedGoogle Scholar
  82. 81.
    Bhatia, S., Curti, B. D., Gordon, M. S., Quinn, D. I., DeVries, T. A., Hunder, N. H., and Thompson, J. A. (2007) Mol Cancer Therapeut 6, 3354SGoogle Scholar
  83. 82.
    Bhatia, S., Curti, B. D., Gordon, M. S., Quinn, D. I., Thompson, J.A., DeVries, T. A., Dodds, M. G., Hunder, N. N., and Hausman, D. F. (2008) J Clin Oncol 26, 16008Google Scholar
  84. 83.
    Lake, R. A., and Robinson, B. W. (2005) Nat Rev Cancer 5, 397PubMedGoogle Scholar
  85. 84.
    Zitvogel, L., Apetoh, L., Ghiringhelli, F., and Kroemer, G. (2008) Nat Rev Immunol 8, 59PubMedGoogle Scholar
  86. 85.
    Ives, N. J., Stowe, R. L., Lorigan, P., and Wheatley, K. (2007) J Clin Oncol 25, 5426PubMedGoogle Scholar
  87. 86.
    Davis, I. D., Jefford, M., Parente, P., and Cebon, J. (2003) J Leukoc Biol 73, 3PubMedGoogle Scholar
  88. 87.
    Nicholaou, T., Ebert, L., Davis, I. D., Robson, N., Klein, O., Maraskovsky, E., Chen, W., and Cebon, J. (2006) Immunol Cell Biol 84, 303PubMedGoogle Scholar
  89. 88.
    He, H., Wisner, P., Yang, G., Hu, H. M., Haley, D., Miller, W., O’Hara, A., Alvord, W. G., Clegg, C. H., Fox, B. A., Urba, W. J., and Walker, E. B. (2006) J Transl Med 4, 24PubMedGoogle Scholar
  90. 89.
    Nakano, H., Kishida, T., Asada, H., Shin-Ya, M., Shinomiya, T., Imanishi, J., Shimada, T., Nakai, S., Takeuchi, M., Hisa, Y., and Mazda, O. (2006) J Gene Med 8, 90PubMedGoogle Scholar
  91. 90.
    Li, Y., and Yee, C. (2008) Blood 111, 229PubMedGoogle Scholar
  92. 91.
    Rosenberg, S. A., Restifo, N. P., Yang, J. C., Morgan, R. A., and Dudley, M. E. (2008) Nat Rev Cancer 8, 299PubMedGoogle Scholar
  93. 92.
    Kirkwood, J. M., Tarhini, A. A., Panelli, M. C., Moschos, S. J., Zarour, H. M., Butterfield, L. H., and Gogas, H. J. (2008) J Clin Oncol 26, 3445PubMedGoogle Scholar
  94. 93.
    Ribas, A. (2006) J Natl Compr Canc Netw 4, 687PubMedGoogle Scholar
  95. 94.
    Peggs, K. S., Quezada, S. A., Korman, A. J., and Allison, J. P. (2006) Curr Opin Immunol 18, 206PubMedGoogle Scholar
  96. 95.
    Barnett, B., Kryczek, I., Cheng, P., Zou, W., and Curiel, T. J. (2005) Am J Reprod Immunol 54, 369PubMedGoogle Scholar
  97. 96.
    Litzinger, M. T., Fernando, R., Curiel, T. J., Grosenbach, D. W., Schlom, J., and Palena, C. (2007) Blood 110, 3192PubMedGoogle Scholar
  98. 97.
    Beck, K. E., Blansfield, J. A., Tran, K. Q., Feldman, A. L., Hughes, M. S., Royal, R. E., Kammula, U. S., Topalian, S. L., Sherry, R. M., Kleiner, D., Quezado, M., Lowy, I., Yellin, M., Rosenberg, S. A., and Yang, J. C. (2006) J Clin Oncol 24, 2283PubMedGoogle Scholar
  99. 98.
    Sanderson, K., Scotland, R., Lee, P., Liu, D., Groshen, S., Snively, J., Sian, S., Nichol, G., Davis, T., Keler, T., Yellin, M., and Weber, J. (2005) J Clin Oncol 23, 741PubMedGoogle Scholar
  100. 99.
    Ribas, A., Camacho, L. H., Lopez-Berestein, G., Pavlov, D., Bulanhagui, C. A., Millham, R., Comin-Anduix, B., Reuben, J. M., Seja, E., Parker, C. A., Sharma, A., Glaspy, J. A., and Gomez-Navarro, J. (2005) J Clin Oncol 23, 8968PubMedGoogle Scholar
  101. 100.
    Maker, A. V., Phan, G. Q., Attia, P., Yang, J. C., Sherry, R. M., Topalian, S. L., Kammula, U. S., Royal, R. E., Haworth, L. R., Levy, C., Kleiner, D., Mavroukakis, S. A., Yellin, M., and Rosenberg, S. A. (2005) Ann Surg Oncol 12, 1005PubMedGoogle Scholar
  102. 101.
    Maker, A. V., Attia, P., and Rosenberg, S. A. (2005) J Immunol 175, 7746PubMedGoogle Scholar
  103. 102.
    Attia, P., Phan, G. Q., Maker, A. V., Robinson, M. R., Quezado, M. M., Yang, J. C., Sherry, R. M., Topalian, S. L., Kammula, U. S., Royal, R. E., Restifo, N. P., Haworth, L. R., Levy, C., Mavroukakis, S. A., Nichol, G., Yellin, M. J., and Rosenberg, S. A. (2005) J Clin Oncol 23, 6043PubMedGoogle Scholar
  104. 103.
    Phan, G. Q., Yang, J. C., Sherry, R. M., Hwu, P., Topalian, S. L., Schwartzentruber, D. J., Restifo, N. P., Haworth, L. R., Seipp, C. A., Freezer, L. J., Morton, K. E., Mavroukakis, S. A., Duray, P. H., Steinberg, S. M., Allison, J. P., Davis, T. A., and Rosenberg, S. A. (2003) Proc Natl Acad Sci USA 100, 8372PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Ian D. Davis
    • 1
  • Kresten Skak
  • Naomi Hunder
  • Mark J. Smyth
  • Pallavur V. Sivakumar
  1. 1.Ludwig-Austin Joint Medical Oncology UnitAustin HealthMelbourneAustralia

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