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Uses of Telomerase Peptides in Anti-Tumor Immune Therapy

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Telomerase Inhibition

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 405))

Summary

Human telomerase reverse transcriptase (hTERT) represents a universal tumor-associated antigen to activate specific immune response in cancer immune therapy. Peptides derived from hTERT are presented by major histocompatibility complex (MHC) class I alleles to T lymphocytes, and CD8+ cytotoxic T lymphocytes (CTLs) specific for the hTERT-derived antigenic epitopes lyse hTERT-positive tumors from multiple histologies. These findings identify hTERT as an important tumor antigen widely applicable for anti-cancer immunotherapeutic strategies. The hTERT antigen-specific immunotherapy involves both active vaccination and adoptive immunotherapy approaches. Most importantly, the anti-tumor immune responses have been observed in the absence of toxicity, underlying the ongoing endeavors to develop immunotherapy directed against hTERT antigen. This chapter discusses most promising results and the approaches for investigation to target hTERT peptides as tumor antigens.

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References

  1. Van Pel, A., van der Bruggen, P., Coulie, P. G., Brichard, V. G., Lethe, B., van den Eynde, B., Uyttenhove, C., Renauld, J. C., and Boon, T. (1995) Genes coding for tumor antigens recognized by cytolytic T lymphocytes. Immunol Rev 145, 229–50.

    Article  PubMed  Google Scholar 

  2. Rosenberg, S. A. (1997) Cancer vaccines based on the identification of genes encoding cancer regression antigens. Immunol Today 18, 175–82.

    Article  CAS  PubMed  Google Scholar 

  3. Vonderheide, R. H., Hahn, W. C., Schultze, J. L., and Nadler, L. M. (1999) The telomerase catalytic subunit is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes. Immunity 10, 673–9.

    Article  CAS  PubMed  Google Scholar 

  4. Rosenberg, S. A. (2001) Progress in human tumour immunology and immunotherapy. Nature 411, 380–4.

    Article  CAS  PubMed  Google Scholar 

  5. Scardino, A., Gross, D. A., Alves, P., Schultze, J. L., Graff-Dubois, S., Faure, O., Tourdot, S., Chouaib, S., Nadler, L. M., Lemonnier, F. A., Vonderheide, R. H., Cardoso, A. A., and Kosmatopoulos, K. (2002) HER-2/neu and hTERT cryptic epitopes as novel targets for broad spectrum tumor immunotherapy. J Immunol 168, 5900–6.

    CAS  PubMed  Google Scholar 

  6. Lev, A., Denkberg, G., Cohen, C. J., Tzukerman, M., Skorecki, K. L., Chames, P., Hoogenboom, H. R., and Reiter, Y. (2002) Isolation and characterization of human recombinant antibodies endowed with the antigen-specific, major histocompatibility complex-restricted specificity of T cells directed toward the widely expressed tumor T-cell epitopes of the telomerase catalytic subunit. Cancer Res 62, 3184–94.

    CAS  PubMed  Google Scholar 

  7. Speiser, D. E., Cerottini, J. C., and Romero, P. (2002) Can hTERT peptide \h{(540-548)}-specific CD8 T cells recognize and kill tumor cells? Cancer Immun 2, 14.

    Google Scholar 

  8. Maecker, B., von Bergwelt-Baildon, M. S., Anderson, K. S., Vonderheide, R. H., Anderson, K. C., Nadler, L. M., and Schultze, J. L. (2005) Rare naturally occurring immune responses to three epitopes from the widely expressed tumour antigens hTERT and CYP1B1 in multiple myeloma patients. Clin Exp Immunol 141, 558–62.

    Article  CAS  PubMed  Google Scholar 

  9. Chen, L. (1998) Immunological ignorance of silent antigens as an explanation of tumor evasion. Immunol Today 19, 27–30.

    Article  CAS  PubMed  Google Scholar 

  10. Ochsenbein, A. F., Klenerman, P., Karrer, U., Ludewig, B., Pericin, M., Hengartner, H., and Zinkernagel, R. M. (1999) Immune surveillance against a solid tumor fails because of immunological ignorance. Proc Natl Acad Sci USA 96, 2233–8.

    Article  CAS  PubMed  Google Scholar 

  11. Lee, P. P., Yee, C., Savage, P. A., Fong, L., Brockstedt, D., Weber, J. S., Johnson, D., Swetter, S., Thompson, J., Greenberg, P. D., Roederer, M., and Davis, M. M. (1999) Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients. Nat Med 5, 677–85.

    Article  CAS  PubMed  Google Scholar 

  12. Ayyoub, M., Migliaccio, M., Guillaume, P., Lienard, D., Cerottini, J. C., Romero, P., Levy, F., Speiser, D. E., and Valmori, D. (2001) Lack of tumor recognition by hTERT peptide 540-548-specific CD8(+) T cells from melanoma patients reveals inefficient antigen processing. Eur J Immunol 31, 2642–51.

    Article  CAS  PubMed  Google Scholar 

  13. Van den Eynde, B. J., and van der Bruggen, P. (1997) T cell defined tumor antigens. Curr Opin Immunol 9, 684–93.

    Article  PubMed  Google Scholar 

  14. Gilboa, E. (1999) The makings of a tumor rejection antigen. Immunity 11, 263–70.

    Article  CAS  PubMed  Google Scholar 

  15. Schultze, J. L., and Vonderheide, R. H. (2001) From cancer genomics to cancer immunotherapy: toward second-generation tumor antigens. Trends Immunol\break22, 516–23.

    Article  CAS  Google Scholar 

  16. Vonderheide, R. H. (2002) Telomerase as a universal tumor-associated antigen for cancer immunotherapy. Oncogene 21, 674–9.

    Article  CAS  PubMed  Google Scholar 

  17. Minev, B., Hipp, J., Firat, H., Schmidt, J. D., Langlade-Demoyen, P., and Zanetti, M. (2000) Cytotoxic T cell immunity against telomerase reverse transcriptase in humans. Proc Natl Acad Sci USA 97, 4796–801.

    Article  CAS  PubMed  Google Scholar 

  18. Vonderheide, R. H., Domchek, S. M., Schultze, J. L., George, D. J., Hoar, K. M., Chen, D. Y., Stephans, K. F., Masutomi, K., Loda, M., Xia, Z., Anderson, K. S., Hahn, W. C., and Nadler, L. M. (2004) Vaccination of cancer patients against telomerase induces functional antitumor CD8+ T lymphocytes. Clin Cancer Res 10, 828–39.

    Article  CAS  PubMed  Google Scholar 

  19. Kosmatopoulos, K., Bolonaki, E., Cornet, S., Nikoloudi, E., Kanellou, P., Millaki, G., Miconnet, I., Christophillakis, C. H., Spiropoulou, M., Georgoulias, V., and Mavroudis, D. (2005) Safety and immunogenicity of the optimized cryptic peptide TERT572Y in patients with advanced malignancies: a phase I clinical study. J Clin Oncol 23, 2005–579.

    Google Scholar 

  20. Kim, N. W., Piatyszek, M. A., Prowse, K. R., Harley, C. B., West, M. D., Ho, P. L., Coviello, G. M., Wright, W. E., Weinrich, S. L., and Shay, J. W. (1994) Specific association of human telomerase activity with immortal cells and cancer. Science 266, 2011–5.

    Article  CAS  PubMed  Google Scholar 

  21. Shay, J. W., and Wright, W. E. (2002) Telomerase: a target for cancer therapeutics. Cancer Cell 2, 257–65.

    Article  CAS  PubMed  Google Scholar 

  22. Hahn, W. C., Stewart, S. A., Brooks, M. W., York, S. G., Eaton, E., Kurachi, A., Beijersbergen, R. L., Knoll, J. H., Meyerson, M., and Weinberg, R. A. (1999) Inhibition of telomerase limits the growth of human cancer cells [see comments]. Nat Med 5, 1164–70.

    Article  CAS  PubMed  Google Scholar 

  23. Greenberg, R. A., Chin, L., Femino, A., Lee, K. H., Gottlieb, G. J., Singer, R. H., Greider, C. W., and DePinho, R. A. (1999) Short dysfunctional telomeres impair tumorigenesis in the INK4a(delta2/3) cancer-prone mouse. Cell 97, 515–25.

    Article  CAS  PubMed  Google Scholar 

  24. Herbert, B., Pitts, A. E., Baker, S. I., Hamilton, S. E., Wright, W. E., Shay, J. W., and Corey, D. R. (1999) Inhibition of human telomerase in immortal human cells leads to progressive telomere shortening and cell death. Proc Natl Acad Sci USA 96, 14276–81.

    Article  CAS  PubMed  Google Scholar 

  25. Bayne, S., and Liu, J. P. (2005) Hormones and growth factors regulate telomerase activity in ageing and cancer. Mol Cell Endocrinol 240, 11–22.

    Article  CAS  PubMed  Google Scholar 

  26. Parmiani, G., Castelli, C., Dalerba, P., Mortarini, R., Rivoltini, L., Marincola, F. M., and Anichini, A. (2002) Cancer immunotherapy with peptide-based vaccines: what have we achieved? Where are we going? J Natl Cancer Inst 94, 805–18.

    Google Scholar 

  27. Nair, S. K., Heiser, A., Boczkowski, D., Majumdar, A., Naoe, M., Lebkowski, J. S., Vieweg, J., and Gilboa, E. (2000) Induction of cytotoxic T cell responses and tumor immunity against unrelated tumors using telomerase reverse transcriptase RNA transfected dendritic cells. Nat Med 6, 1011–7.

    Article  CAS  PubMed  Google Scholar 

  28. Prowse, K. R., and Greider, C. W. (1995) Developmental and tissue-specific regulation of mouse telomerase and telomere length. Proc Natl Acad Sci USA 92, 4818–22.

    Article  CAS  PubMed  Google Scholar 

  29. Hernandez, J., Garcia-Pons, F., Lone, Y. C., Firat, H., Schmidt, J. D., Langlade-Demoyen, P., and Zanetti, M. (2002) Identification of a human telomerase reverse transcriptase peptide of low affinity for HLA A2.1 that induces cytotoxic T lymphocytes and mediates lysis of tumor cells. Proc Natl Acad Sci USA 99,\break 12275–80.

    Article  CAS  PubMed  Google Scholar 

  30. Vonderheide, R. H., Anderson, K. S., Hahn, W. C., Butler, M. O., Schultze, J. L., and Nadler, L. M. (2001) Characterization of HLA-A3-restricted cytotoxic T lymphocytes reactive against the widely expressed tumor antigen telomerase. Clin Cancer Res 7, 3343–8.

    CAS  PubMed  Google Scholar 

  31. Tokunaga, K., Ishikawa, Y., Ogawa, A., Wang, H., Mitsunaga, S., Moriyama, S., Lin, L., Bannai, M., Watanabe, Y., Kashiwase, K., Tanaka, H., Akaza, T., Tadokoro, K., and Juji, T. (1997) Sequence-based association analysis of HLA class I and II alleles in Japanese supports conservation of common haplotypes. Immunogenetics 46, 199–205.

    Article  CAS  PubMed  Google Scholar 

  32. Arai, J., Yasukawa, M., Ohminami, H., Kakimoto, M., Hasegawa, A., and Fujita, S. (2001) Identification of human telomerase reverse transcriptase-derived peptides that induce HLA-A24-restricted antileukemia cytotoxic T lymphocytes. Blood 97, 2903–7.

    Article  CAS  PubMed  Google Scholar 

  33. Vonderheide, R. H., Schultze, J. L., Anderson, K. S., Maecker, B., Butler, M. O., Xia, Z., Kuroda, M. J., von Bergwelt-Baildon, M. S., Bedor, M. M., Hoar, K. M., Schnipper, D. R., Brooks, M. W., Letvin, N. L., Stephans, K. F., Wucherpfennig, K. W., Hahn, W. C., and Nadler, L. M. (2001) Equivalent induction of telomerase-specific cytotoxic T lymphocytes from tumor-bearing patients and healthy individuals. Cancer Res 61, 8366–70.

    CAS  PubMed  Google Scholar 

  34. Harle-Bachor, C., and Boukamp, P. (1996) Telomerase activity in the regenerative basal layer of the epidermis inhuman skin and in immortal and carcinoma-derived skin keratinocytes. Proc Natl Acad Sci USA 93, 6476–81.

    Article  CAS  PubMed  Google Scholar 

  35. Yasumoto, S., Kunimura, C., Kikuchi, K., Tahara, H., Ohji, H., Yamamoto, H., Ide, T., and Utakoji, T. (1996) Telomerase activity in normal human epithelial cells. Oncogene 13, 433–9.

    CAS  PubMed  Google Scholar 

  36. Kolquist, K. A., Ellisen, L. W., Counter, C. M., Meyerson, M., Tan, L. K., Weinberg, R. A., Haber, D. A., and Gerald, W. L. (1998) Expression of TERT in early premalignant lesions and a subset of cells in normal tissues [see comments]. Nat Genet 19, 182–6.

    Article  CAS  PubMed  Google Scholar 

  37. Norrback, K. F., and Roos, G. (1997) Telomeres and telomerase in normal and malignant haematopoietic cells. Eur J Cancer 33, 774–80.

    Article  CAS  PubMed  Google Scholar 

  38. Masutomi, K., Yu, E. Y., Khurts, S., Ben-Porath, I., Currier, J. L., Metz, G. B., Brooks, M. W., Kaneko, S., Murakami, S., DeCaprio, J. A., Weinberg, R. A., Stewart, S. A., and Hahn, W. C. (2003) Telomerase maintains telomere structure in normal human cells. Cell 114, 241–53.

    Article  CAS  PubMed  Google Scholar 

  39. Dhodapkar, M. V., Steinman, R. M., Sapp, M., Desai, H., Fossella, C., Krasovsky, J., Donahoe, S. M., Dunbar, P. R., Cerundolo, V., Nixon, D. F., and Bhardwaj, N. (1999) Rapid generation of broad T-cell immunity in humans after a single injection of mature dendritic cells. J Clin Invest 104, 173–80.

    Article  CAS  PubMed  Google Scholar 

  40. Banchereau, J., Palucka, A. K., Dhodapkar, M., Burkeholder, S., Taquet, N., Rolland, A., Taquet, S., Coquery, S., Wittkowski, K. M., Bhardwaj, N., Pineiro, L., Steinman, R., and Fay, J. (2001) Immune and clinical responses in patients with metastatic melanoma to CD34(+) progenitor-derived dendritic cell vaccine. Cancer Res 61, 6451–8.

    CAS  PubMed  Google Scholar 

  41. Gilliet, M., Kleinhans, M., Lantelme, E., Schadendorf, D., Burg, G., and Nestle, F. O. (2003) Intranodal injection of semimature monocyte-derived dendritic cells induces T helper type 1 responses to protein neoantigen. Blood 102, 36–42.

    Article  CAS  PubMed  Google Scholar 

  42. Jonuleit, H., Giesecke-Tuettenberg, A., Tuting, T., Thurner-Schuler, B., Stuge, T. B., Paragnik, L., Kandemir, A., Lee, P. P., Schuler, G., Knop, J., and Enk, A. H. (2001) A comparison of two types of dendritic cell as adjuvants for the induction of melanoma-specific T-cell responses in humans following intranodal injection. Int J Cancer 93, 243–51.

    Article  CAS  PubMed  Google Scholar 

  43. De Vries, I. J., Krooshoop, D. J., Scharenborg, N. M., Lesterhuis, W. J., Diepstra, J. H., Van Muijen, G. N., Strijk, S. P., Ruers, T. J., Boerman, O. C., Oyen, W. J., Adema, G. J., Punt, C. J., and Figdor, C. G. (2003) Effective migration of antigen-pulsed dendritic cells to lymph nodes in melanoma patients is determined by their maturation state. Cancer Res 63, 12–7.

    PubMed  Google Scholar 

  44. Nestle, F. O., Alijagic, S., Gilliet, M., Sun, Y., Grabbe, S., Dummer, R., Burg, G., and Schadendorf, D. (1998) Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat Med 4, 328–32.

    Article  CAS  PubMed  Google Scholar 

  45. Dhodapkar, M. V., Steinman, R. M., Krasovsky, J., Munz, C., and Bhardwaj, N. (2001) Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J Exp Med 193, 233–8.

    Article  CAS  PubMed  Google Scholar 

  46. Dudley, M. E., Wunderlich, J. R., Robbins, P. F., Yang, J. C., Hwu, P., Schwartzentruber, D. J., Topalian, S. L., Sherry, R., Restifo, N. P., Hubicki, A. M., Robinson, M. R., Raffeld, M., Duray, P., Seipp, C. A., Rogers-Freezer, L., Morton, K. E., Mavroukakis, S. A., White, D. E., and Rosenberg, S. A. (2002) Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 298, 850–4.

    Article  CAS  PubMed  Google Scholar 

  47. DiBrino, M., Parker, K. C., Shiloach, J., Knierman, M., Lukszo, J., Turner, R. V., Biddison, W. E., and Coligan, J. E. (1993) Endogenous peptides bound to HLA-A3 possess a specific combination of anchor residues that permit identification of potential antigenic peptides. Proc Natl Acad Sci USA 90, 1508–12.

    Article  CAS  PubMed  Google Scholar 

  48. DiBrino, M., Tsuchida, T., Turner, R. V., Parker, K. C., Coligan, J. E., and Biddison, W. E. (1993) HLA-A1 and HLA-A3 T cell epitopes derived from influenza virus proteins predicted from peptide binding motifs. J Immunol 151, 5930–5.

    CAS  PubMed  Google Scholar 

  49. Tsomides, T. J., Walker, B. D., and Eisen, H. N. (1991) An optimal viral peptide recognized by CD8+ T cells binds very tightly to the restricting class I major histocompatibility complex protein on intact cells but not to the purified class I protein. Proc Natl Acad Sci USA 88, 11276–80.

    Article  CAS  PubMed  Google Scholar 

  50. Tanaka, F., Fujie, T., Tahara, K., Mori, M., Takesako, K., Sette, A., Celis, E., and Akiyoshi, T. (1997) Induction of antitumor cytotoxic T lymphocytes with a MAGE-3-encoded synthetic peptide presented by human leukocytes antigen-A24. Cancer Res 57, 4465–8.

    CAS  PubMed  Google Scholar 

  51. Pascolo, S., Bervas, N., Ure, J. M., Smith, A. G., Lemonnier, F. A., and Perarnau, B. (1997) HLA-A2.1-restricted education and cytolytic activity of CD8(+) T lymphocytes from beta2 microglobulin (beta2m) HLA-A2.1 monochain transgenic H-2Db beta2m double knockout mice. J Exp Med 185, 2043–51.

    Article  CAS  PubMed  Google Scholar 

  52. Congia, M., Patel, S., Cope, A. P., De Virgiliis, S., and Sonderstrup, G. (1998) T cell epitopes of insulin defined in HLA-DR4 transgenic mice are derived from preproinsulin and proinsulin. Proc Natl Acad Sci USA 95, 3833–8.

    Article  CAS  PubMed  Google Scholar 

  53. Sonderstrup, G., and McDevitt, H. (1998) Identification of autoantigen epitopes in MHC class II transgenic mice. Immunol Rev 164, 129–38.

    Article  CAS  PubMed  Google Scholar 

  54. Sonderstrup, G., Cope, A. P., Patel, S., Congia, M., Hain, N., Hall, F. C., Parry, S. L., Fugger, L. H., Michie, S., and McDevitt, H. O. (1999) HLA class II transgenic mice: models of the human CD4+ T-cell immune response. Immunol Rev 172, 335–43.

    Article  CAS  PubMed  Google Scholar 

  55. Ruppert, J., Sidney, J., Celis, E., Kubo, R. T., Grey, H. M., and Sette, A. (1993) Prominent role of secondary anchor residues in peptide binding to HLA-A2.1 molecules. Cell 74, 929–37.

    Article  CAS  PubMed  Google Scholar 

  56. Krausa, P., Brywka, M., 3rd, Savage, D., Hui, K. M., Bunce, M., Ngai, J. L., Teo, D. L., Ong, Y. W., Barouch, D., Allsop, C. E., and et al. (1995) Genetic polymorphism within HLA-A*02: significant allelic variation revealed in different populations. Tissue Antigens 45, 223–31.

    Article  CAS  PubMed  Google Scholar 

  57. Parker, K. C., Bednarek, M. A., and Coligan, J. E. (1994) Scheme for ranking potential HLA-A2 binding peptides based on independent binding of individual peptide side-chains. J Immunol 152, 163–75.

    CAS  PubMed  Google Scholar 

  58. Firat, H., Garcia-Pons, F., Tourdot, S., Pascolo, S., Scardino, A., Garcia, Z., Michel, M. L., Jack, R. W., Jung, G., Kosmatopoulos, K., Mateo, L., Suhrbier, A., Lemonnier, F. A., and Langlade-Demoyen, P. (1999) H-2 class I knockout, HLA-A2.1-transgenic mice: a versatile animal model for preclinical evaluation of antitumor immunotherapeutic strategies. Eur J Immunol 29, 3112–21.

    Article  CAS  PubMed  Google Scholar 

  59. Altman, J. D., Moss, P. A., Goulder, P. J., Barouch, D. H., McHeyzer-Williams, M. G., Bell, J. I., McMichael, A. J., and Davis, M. M. (1996) Phenotypic analysis of antigen-specific T lymphocytes. Science 274, 94–6.

    Article  CAS  PubMed  Google Scholar 

  60. Kannagi, M., Shida, H., Igarashi, H., Kuruma, K., Murai, H., Aono, Y., Maruyama, I., Osame, M., Hattori, T., Inoko, H., and et al. (1992) Target epitope in the Tax protein of human T-cell leukemia virus type I recognized by class I major histocompatibility complex-restricted cytotoxic T cells. J Virol 66, 2928–33.

    CAS  PubMed  Google Scholar 

  61. Schultze, J. L., Seamon, M. J., Michalak, S., Gribben, J. G., and Nadler, L. M. (1997) Autologous tumor infiltrating T cells cytotoxic for follicular lymphoma cells can be expanded in vitro. Blood 89, 3806–16.

    CAS  PubMed  Google Scholar 

  62. Schultze, J. L., Cardoso, A. A., Freeman, G. J., Seamon, M. J., Daley, J., Pinkus, G. S., Gribben, J. G., and Nadler, L. M. (1995) Follicular lymphomas can be induced to present alloantigen efficiently: a conceptual model to improve their tumor immunogenicity. Proc Natl Acad Sci USA 92, 8200–4.

    Article  CAS  PubMed  Google Scholar 

  63. Schultze, J. L., Michalak, S., Seamon, M. J., Dranoff, G., Jung, K., Daley, J., Delgado, J. C., Gribben, J. G., and Nadler, L. M. (1997) CD40-activated human B cells: an alternative source of highly efficient antigen presenting cells to generate autologous antigen-specific T cells for adoptive immunotherapy. J Clin Invest 100, 2757–65.

    Article  CAS  PubMed  Google Scholar 

  64. Romani, N., Reider, D., Heuer, M., Ebner, S., Kampgen, E., Eibl, B., Niederwieser, D., and Schuler, G. (1996) Generation of mature dendritic cells from human blood. An improved method with special regard to clinical applicability. J Immunol Methods 196, 137–51.

    Article  CAS  PubMed  Google Scholar 

  65. Yssel, H., De Vries, J. E., Koken, M., Van Blitterswijk, W., and Spits, H. (1984) Serum-free medium for generation and propagation of functional human cytotoxic and helper T cell clones. J Immunol Methods 72, 219–27.

    Article  CAS  PubMed  Google Scholar 

  66. Schreurs, M. W., Scholten, K. B., Kueter, E. W., Ruizendaal, J. J., Meijer, C. J., and Hooijberg, E. (2003) In vitro generation and life span extension of human papillomavirus type 16-specific, healthy donor-derived CTL clones. J Immunol 171, 2912–21.

    CAS  PubMed  Google Scholar 

  67. Matzinger, P. (1991) The JAM test. A simple assay for DNA fragmentation and cell death. J Immunol Methods 145, 185–92.

    Article  CAS  PubMed  Google Scholar 

  68. Geluk, A., Taneja, V., van Meijgaarden, K. E., de Vries, R. R., David, C. S., and Ottenhoff, T. H. (1998) HLA-DR/DQ transgenic, class II deficient mice as a novel model to select for HSP T cell epitopes with immunotherapeutic or preventative vaccine potential. Biotherapy 10, 191–6.

    Article  PubMed  Google Scholar 

  69. Parkhurst, M. R., Riley, J. P., Igarashi, T., Li, Y., Robbins, P. F., and Rosenberg, S. A. (2004) Immunization of patients with the hTERT:540-548 peptide induces peptide-reactive T lymphocytes that do not recognize tumors endogenously expressing telomerase. Clin Cancer Res 10, 4688–98.

    Article  CAS  PubMed  Google Scholar 

  70. Rosenberg, S. A., Yang, J. C., Schwartzentruber, D. J., Hwu, P., Marincola, F. M., Topalian, S. L., Restifo, N. P., Dudley, M. E., Schwarz, S. L., Spiess, P. J., Wunderlich, J. R., Parkhurst, M. R., Kawakami, Y., Seipp, C. A., Einhorn, J. H., and White, D. E. (1998) Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma. Nat Med 4, 321–7.

    Article  CAS  PubMed  Google Scholar 

  71. Bordignon, C., Notarangelo, L. D., Nobili, N., Ferrari, G., Casorati, G., Panina, P., Mazzolari, E., Maggioni, D., Rossi, C., Servida, P., Ugazio, A. G., and Mavilio, F. (1995) Gene therapy in peripheral blood lymphocytes and bone marrow for ADA-immunodeficient patients. Science 270, 470–5.

    Article  CAS  PubMed  Google Scholar 

  72. Heemskerk, M. H., Hooijberg, E., Ruizendaal, J. J., van der Weide, M. M., Kueter, E., Bakker, A. Q., Schumacher, T. N., and Spits, H. (1999) Enrichment of an antigen-specific T cell response by retrovirally transduced human dendritic cells. Cell Immunol 195, 10–7.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

The work was supported by grants from the Australia Research Council and National Health & Medical Research Council of Australia.

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Li, H., Katik, I., Liu, JP. (2007). Uses of Telomerase Peptides in Anti-Tumor Immune Therapy. In: Andrews, L.G., Tollefsbol, T.O. (eds) Telomerase Inhibition. Methods in Molecular Biology™, vol 405. Humana Press. https://doi.org/10.1007/978-1-60327-070-0_7

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  • DOI: https://doi.org/10.1007/978-1-60327-070-0_7

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