Skip to main content
SpringerLink
Log in

Identification of Tumor Antigens as Targets for Novel Antitumor Therapies

  • Chapter
  • First Online:
New Advances on Disease Biomarkers and Molecular Targets in Biomedicine

  • 968 Accesses

Abstract

Cancer is still one of the leading causes of death at present. The development of immunotherapies based on the identification of tumor antigens provides a promising option of cancer therapy. Tumor antigens are the targets that could be recognized by T cells or antibodies and thus elicit immune response in cancer patients. Since tumor antigens are exclusively expressed or over expressed on tumor cells, the immune responses against tumor antigens would only destroy tumor cells but not normal cells. Cancer immunotherapies discussed in this chapter refer to therapeutic monoclonal antibodies, adoptive T cell therapy, and therapeutic vaccines. With the superiority of high specificity, cancer immunotherapies may act as a personalized treatment against cancer to overcome the immune suppression environment of cancer patients as well as the unexpected side effects.

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 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
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. Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD (2002) Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 3:991–998

    Article  PubMed  CAS  Google Scholar 

  2. Dunn GP, Old LJ, Schreiber RD (2004) The three Es of cancer immunoediting. Annu Rev Immunol 22:329–360

    Article  PubMed  CAS  Google Scholar 

  3. Swann JB, Smyth MJ (2007) Immune surveillance of tumors. J Clin Invest 117:1137–1146

    Article  PubMed  CAS  Google Scholar 

  4. Burnet FM (1970) The concept of immunological surveillance. Prog Exp Tumor Res 13:1–27

    PubMed  CAS  Google Scholar 

  5. Stutman O (1974) Tumor development after 3-methylcholanthrene in immunologically deficient athymic-nude mice. Science 183:534–536

    Article  PubMed  CAS  Google Scholar 

  6. Stutman O (1979) Chemical carcinogenesis in nude mice: comparison between nude mice from homozygous matings and heterozygous matings and effect of age and carcinogen dose. J Natl Cancer Inst 62:353–358

    PubMed  CAS  Google Scholar 

  7. Maleckar JR, Sherman LA (1987) The composition of the T cell receptor repertoire in nude mice. J Immunol 138:3873–3876

    PubMed  CAS  Google Scholar 

  8. Ikehara S, Pahwa RN, Fernandes G, Hansen CT, Good RA (1984) Functional T cells in athymic nude mice. Proc Natl Acad Sci USA 81:886–888

    Article  PubMed  CAS  Google Scholar 

  9. Herberman RB, Holden HT (1978) Natural cell-mediated immunity. Adv Cancer Res 27:305–377

    Article  PubMed  CAS  Google Scholar 

  10. Smyth MJ, Crowe NY, Godfrey DI (2001) NK cells and NKT cells collaborate in host protection from methylcholanthrene-induced fibrosarcoma. Int Immunol 13:459–463

    Article  PubMed  CAS  Google Scholar 

  11. 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 410:1107–1111

    Article  PubMed  CAS  Google Scholar 

  12. Street SE, Cretney E, Smyth MJ (2001) Perforin and interferon-gamma activities independently control tumor initiation, growth, and metastasis. Blood 97:192–197

    Article  PubMed  CAS  Google Scholar 

  13. Street SE, Trapani JA, MacGregor D, Smyth MJ (2002) Suppression of lymphoma and epithelial malignancies effected by interferon gamma. J Exp Med 196:129–134

    Article  PubMed  CAS  Google Scholar 

  14. Smyth MJ, Thia KY, Street SE, Cretney E, Trapani JA, Taniguchi M, Kawano T, Pelikan SB, Crowe NY, Godfrey DI (2000) Differential tumor surveillance by natural killer (NK) and NKT cells. J Exp Med 191:661–668

    Article  PubMed  CAS  Google Scholar 

  15. Penn I, Starzl TE (1970) Malignant lymphomas in transplantation patients: a review of the world experience. Int Z Klin Pharmakol Ther Toxikol 3:49–54

    PubMed  CAS  Google Scholar 

  16. Gatti RA, Good RA (1971) Occurrence of malignancy in immunodeficiency diseases. A literature review. Cancer 28:89–98

    Article  PubMed  CAS  Google Scholar 

  17. Boshoff C, Weiss R (2002) AIDS-related malignancies. Nat Rev Cancer 2:373–382

    Article  PubMed  CAS  Google Scholar 

  18. Pham SM, Kormos RL, Landreneau RJ, Kawai A, Gonzalez-Cancel I, Hardesty RL, Hattler BG, Griffith BP (1995) Solid tumors after heart transplantation: lethality of lung cancer. Ann Thorac Surg 60:1623–1626

    Article  PubMed  CAS  Google Scholar 

  19. Penn I (1996) Malignant melanoma in organ allograft recipients. Transplantation 61:274–278

    Article  PubMed  CAS  Google Scholar 

  20. Clemente CG, Mihm MC Jr, Bufalino R, Zurrida S, Collini P, Cascinelli N (1996) Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma. Cancer 77:1303–1310

    Article  PubMed  CAS  Google Scholar 

  21. Mihm MC Jr, Clemente CG, Cascinelli N (1996) Tumor infiltrating lymphocytes in lymph node melanoma metastases: a histopathologic prognostic indicator and an expression of local immune response. Lab Invest 74:43–47

    PubMed  Google Scholar 

  22. Ikeda H, Lethe B, Lehmann F, van Baren N, Baurain JF, de Smet C, Chambost H, Vitale M, Moretta A, Boon T, Coulie PG (1997) Characterization of an antigen that is recognized on a melanoma showing partial HLA loss by CTL expressing an NK inhibitory receptor. Immunity 6:199–208

    Article  PubMed  CAS  Google Scholar 

  23. Koopman LA, Corver WE, van der Slik AR, Giphart MJ, Fleuren GJ (2000) Multiple genetic alterations cause frequent and heterogeneous human histocompatibility leukocyte antigen class I loss in cervical cancer. J Exp Med 191:961–976

    Article  PubMed  CAS  Google Scholar 

  24. Ochsenbein AF, Sierro S, Odermatt B, Pericin M, Karrer U, Hermans J, Hemmi S, Hengartner H, Zinkernagel RM (2001) Roles of tumour localization, second signals and cross priming in cytotoxic T-cell induction. Nature 411:1058–1064

    Article  PubMed  CAS  Google Scholar 

  25. Tada T, Ohzeki S, Utsumi K, Takiuchi H, Muramatsu M, Li XF, Shimizu J, Fujiwara H, Hamaoka T (1991) Transforming growth factor-beta-induced inhibition of T cell function. Susceptibility difference in T cells of various phenotypes and functions and its relevance to immunosuppression in the tumor-bearing state. J Immunol 146:1077–1082

    PubMed  CAS  Google Scholar 

  26. Wang HY, Lee DA, Peng G, Guo Z, Li Y, Kiniwa Y, Shevach EM, Wang RF (2004) Tumor-specific human CD4+ regulatory T cells and their ligands: implications for immunotherapy. Immunity 20:107–118

    Article  PubMed  CAS  Google Scholar 

  27. Eid J, Fehr A, Gray J, Luong K, Lyle J, Otto G, Peluso P, Rank D, Baybayan P, Bettman B, Bibillo A, Bjornson K, Chaudhuri B, Christians F, Cicero R, Clark S, Dalal R, Dewinter A, Dixon J, Foquet M, Gaertner A, Hardenbol P, Heiner C, Hester K, Holden D, Kearns G, Kong X, Kuse R, Lacroix Y, Lin S, Lundquist P, Ma C, Marks P, Maxham M, Murphy D, Park I, Pham T, Phillips M, Roy J, Sebra R, Shen G, Sorenson J, Tomaney A, Travers K, Trulson M, Vieceli J, Wegener J, Wu D, Yang A, Zaccarin D, Zhao P, Zhong F, Korlach J, Turner S (2009) Real-time DNA sequencing from single polymerase molecules. Science 323:133–138

    Article  PubMed  CAS  Google Scholar 

  28. Bubenik J, Perlmann P, Helmstein K, Moberger G (1970) Cellular and humoral immune responses to human urinary bladder carcinomas. Int J Cancer 5:310–319

    Article  PubMed  CAS  Google Scholar 

  29. Blanton SH, Cortez A, Stal S, Mulliken JB, Finnell RH, Hecht JT (2005) Variation in IRF6 contributes to nonsyndromic cleft lip and palate. Am J Med Genet 137A:259–262

    Article  PubMed  Google Scholar 

  30. van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, Knuth A, Boon T (1991) A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science 254:1643–1647

    Article  PubMed  Google Scholar 

  31. Rosenberg SA (1996) Development of cancer immunotherapies based on identification of the genes encoding cancer regression antigens. J Natl Cancer Inst 88:1635–1644

    Article  PubMed  CAS  Google Scholar 

  32. Rosenberg SA (1999) A new era for cancer immunotherapy based on the genes that encode cancer antigens. Immunity 10:281–287

    Article  PubMed  CAS  Google Scholar 

  33. Graziano DF, Finn OJ (2005) Tumor antigens and tumor antigen discovery. Cancer Treat Res 123:89–111

    Article  PubMed  CAS  Google Scholar 

  34. Sahin U, Tureci O, Pfreundschuh M (1997) Serological identification of human tumor antigens. Curr Opin Immunol 9:709–716

    Article  PubMed  CAS  Google Scholar 

  35. Chen YT, Stockert E, Jungbluth A, Tsang S, Coplan KA, Scanlan MJ, Old LJ (1996) Serological analysis of Melan-A(MART-1), a melanocyte-specific protein homogeneously expressed in human melanomas. Proc Natl Acad Sci USA 93:5915–5919

    Article  PubMed  CAS  Google Scholar 

  36. Cox AL, Skipper J, Chen Y, Henderson RA, Darrow TL, Shabanowitz J, Engelhard VH, Hunt DF, Slingluff CL Jr (1994) Identification of a peptide recognized by five melanoma-specific human cytotoxic T cell lines. Science 264:716–719

    Article  PubMed  CAS  Google Scholar 

  37. Castelli C, Storkus WJ, Maeurer MJ, Martin DM, Huang EC, Pramanik BN, Nagabhushan TL, Parmiani G, Lotze MT (1995) Mass spectrometric identification of a naturally processed melanoma peptide recognized by CD8+ cytotoxic T lymphocytes. J Exp Med 181:363–368

    Article  PubMed  CAS  Google Scholar 

  38. Schirle M, Keilholz W, Weber B, Gouttefangeas C, Dumrese T, Becker HD, Stevanovic S, Rammensee HG (2000) Identification of tumor-associated MHC class I ligands by a novel T cell-independent approach. Eur J Immunol 30:2216–2225

    Article  PubMed  CAS  Google Scholar 

  39. Kao H, Amoscato AA, Ciborowski P, Finn OJ (2001) A new strategy for tumor antigen discovery based on in vitro priming of naive T cells with dendritic cells. Clin Cancer Res 7:773s–780s

    PubMed  CAS  Google Scholar 

  40. Finn OJ (2008) Cancer immunology. N Eng J Med 358:2704–2715

    Article  CAS  Google Scholar 

  41. Theobald M, Biggs J, Hernandez J, Lustgarten J, Labadie C, Sherman LA (1997) Tolerance to p53 by A2.1-restricted cytotoxic T lymphocytes. J Exp Med 185:833–841

    Article  PubMed  CAS  Google Scholar 

  42. Wolfel T, Hauer M, Schneider J, Serrano M, Wolfel C, Klehmann-Hieb E, De Plaen E, Hankeln T, Meyer zum Buschenfelde KH, Beach D (1995) A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma. Science 269:1281–1284

    Article  PubMed  CAS  Google Scholar 

  43. Urban JL, Schreiber H (1992) Tumor antigens. Annu Rev Immunol 10:617–644

    Article  PubMed  CAS  Google Scholar 

  44. Morris EC, Bendle GM, Stauss HJ (2003) Prospects for immunotherapy of malignant disease. Clin Exp Immunol 131:1–7

    Article  PubMed  CAS  Google Scholar 

  45. Ho WY, Blattman JN, Dossett ML, Yee C, Greenberg PD (2003) Adoptive immunotherapy: engineering T cell responses as biologic weapons for tumor mass destruction. Cancer Cell 3:431–437

    Article  PubMed  CAS  Google Scholar 

  46. Coulie PG, Brichard V, Van Pel A, Wolfel T, Schneider J, Traversari C, Mattei S, De Plaen E, Lurquin C, Szikora JP, Renauld JC, Boon T (1994) A new gene coding for a differentiation antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J Exp Med 180:35–42

    Article  PubMed  CAS  Google Scholar 

  47. Kawakami Y, Eliyahu S, Delgado CH, Robbins PF, Sakaguchi K, Appella E, Yannelli JR, Adema GJ, Miki T, Rosenberg SA (1994) Identification of a human melanoma antigen recognized by tumor-infiltrating lymphocytes associated with in vivo tumor rejection. Proc Natl Acad Sci USA 91:6458–6462

    Article  PubMed  CAS  Google Scholar 

  48. Brichard V, Van Pel A, Wolfel T, Wolfel C, De Plaen E, Lethe B, Coulie P, Boon T (1993) The tyrosinase gene codes for an antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J Exp Med 178:489–495

    Article  PubMed  CAS  Google Scholar 

  49. Rosenberg SA (1995) The development of new cancer therapies based on the molecular identification of cancer regression antigens. Cancer J Sci Am 1:90–100

    PubMed  CAS  Google Scholar 

  50. Theoret MR, Cohen CJ, Nahvi AV, Ngo LT, Suri KB, Powell DJ Jr, Dudley ME, Morgan RA, Rosenberg SA (2008) Relationship of p53 overexpression on cancers and recognition by anti-p53 T cell receptor-transduced T cells. Hum Gene Ther 19:1219–1232

    Article  PubMed  CAS  Google Scholar 

  51. Chapman PB (2004) T-cell chauvinists versus antibody advocates–can’t we all just get along? J Clin Oncol 22:4446–4448

    Article  PubMed  Google Scholar 

  52. Chames P, Van Regenmortel M, Weiss E, Baty D (2009) Therapeutic antibodies: successes, limitations and hopes for the future. Br J Pharmacol 157:220–233

    Article  PubMed  CAS  Google Scholar 

  53. Adams GP, Weiner LM (2005) Monoclonal antibody therapy of cancer. Nat Biotechnol 23:1147–1157

    Article  PubMed  CAS  Google Scholar 

  54. Rosenberg SA, Packard BS, Aebersold PM, Solomon D, Topalian SL, Toy ST, Simon P, Lotze MT, Yang JC, Seipp CA et al (1988) Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. N Engl J Med 319:1676–1680

    Article  PubMed  CAS  Google Scholar 

  55. Rosenberg SA, Restifo NP, Yang JC, Morgan RA, Dudley ME (2008) Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nat Rev Cancer 8:299–308

    Article  PubMed  CAS  Google Scholar 

  56. Disis ML, Bernhard H, Jaffee EM (2009) Use of tumour-responsive T cells as cancer treatment. Lancet 373:673–683

    Article  PubMed  CAS  Google Scholar 

  57. Emens LA, Reilly RT, Jaffee EM (2005) Cancer vaccines in combination with multimodality therapy. Cancer Treat Res 123:227–245

    Article  PubMed  CAS  Google Scholar 

  58. Dougan M, Dranoff G (2009) Immune therapy for cancer. Annu Rev Immunol 27:83–117

    Article  PubMed  CAS  Google Scholar 

  59. Presta LG (2008) Molecular engineering and design of therapeutic antibodies. Curr Opin Immunol 20:460–470

    Article  PubMed  CAS  Google Scholar 

  60. Masuda K, Kubota T, Kaneko E, Iida S, Wakitani M, Kobayashi-Natsume Y, Kubota A, Shitara K, Nakamura K (2007) Enhanced binding affinity for FcgammaRIIIa of fucose-negative antibody is sufficient to induce maximal antibody-dependent cellular cytotoxicity. Mol Immunol 44:3122–3131

    Article  PubMed  CAS  Google Scholar 

  61. Baeuerle PA, Kufer P, Bargou R (2009) BiTE: Teaching antibodies to engage T-cells for cancer therapy. Curr Opin Mol Ther 11:22–30

    PubMed  CAS  Google Scholar 

  62. Abken H, Hombach A, Heuser C, Reinhold U (2001) A novel strategy in the elimination of disseminated melanoma cells: chimeric receptors endow T cells with tumor specificity. Recent Results Cancer Res 158:249–264

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, Jinan University, Guangzhou, 510632, P.R. China

    Yanyan Han & Qing-Yu He

  2. Department of Biochemistry & Molecular Biology, College of Life Science and Technology, Jinan University, 601 Huangpu Ave. West, Guangzhou, 510632, P.R. China

    Qing-Yu He

Authors
  1. Yanyan Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qing-Yu He
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qing-Yu He .

Editor information

Editors and Affiliations

  1. Faculty of Medicine Building, Department of Surgery, University of Hong Kong, Sassoon Road 21, Hong Kong, Hong Kong SAR

    Nikki P. Lee

  2. Center for Biomedical Research, Population Council, York Ave. 1230, NEW YORK, 10021, New York, USA

    C.Y. Cheng

  3. Yong Loo Lin School of Medicine, Department of Pharmacology and Departmen, National University of Singapore, Medical Drive 10, Singapore, 117597, Singapore

    John M. Luk

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Han, Y., He, QY. (2013). Identification of Tumor Antigens as Targets for Novel Antitumor Therapies. In: Lee, N., Cheng, C., Luk, J. (eds) New Advances on Disease Biomarkers and Molecular Targets in Biomedicine. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-456-2_12

Download citation

Publish with us

Policies and ethics

Search

Navigation