Leader

Immune responses to tumour antigens: implications for antigen specific immunotherapy of cancer

D Jäger, E Jäger and A Knuth

II. Medizinische Klinik, Hämatologie-Onkologie, Krankenhaus Nordwest, Steinbacher Hohl 2–26, 60488 Frankfurt am Main, Germany

Correspondence to:
Dr E Jäger EJ200161{at}aol.com

Tumour associated antigens recognised by cellular or humoral effectors of the immune system are potential targets for antigen specific cancer immunotherapy. Different categories of cancer antigens have been identified that induce cytotoxic T lymphocyte (CTL) responses in vitro and in vivo, namely: (1) "cancer testis" (CT) antigens, expressed in different tumours and normal testis, (2) melanocyte differentiation antigens, (3) point mutations of normal genes, (4) self antigens that are overexpressed in malignant tissues, and (5) viral antigens. Clinical studies with peptides and proteins derived from these antigens have been initiated to study the efficacy of inducing specific CTL responses in vivo. Immunological and clinical parameters for the assessment of antigen specific immune responses have been defined—delayed type hypersensitivity (DTH), CTL, autoimmmune, and tumour regression responses. Specific DTH and CTL responses and tumour regression have been observed after the intradermal administration of tumour associated peptides alone. Peptide specific immune reactions were enhanced after using granulocyte macrophage stimulating factor (GM-CSF) as a systemic adjuvant by increasing the frequency of dermal antigen presenting Langerhans cells. Complete tumour regression has been observed in the context of measurable peptide specific CTL. However, in single cases with disease progression after an initial tumour response, either a loss of single antigens targeted by CTL or of the presenting major histocompatibility complex (MHC) class I allele was detected, pointing towards immunisation induced immune escape. Cytokines to modulate antigen and MHC class I expression in vivo are being evaluated to prevent immunoselection. Recently, a new CT antigen, NY-ESO-1, has been identified on the basis of spontaneous antibody responses to tumour associated antigens. NY-ESO-1 appears to be one of the most immunogenic antigens known to date, with spontaneous immune responses observed in 50% of patients with NY-ESO-1 expressing cancers. Clinical studies have been initiated to evaluate the immunogenicity of different NY-ESO-1 constructs to induce both humoral and cellular immune responses in vivo.

Key Words: tumour antigens • antigen specific T cell response

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Bramswig, K. H., Knittelfelder, R., Gruber, S., Untersmayr, E., Riemer, A. B., Szalai, K., Horvat, R., Kammerer, R., Zimmermann, W., Zielinski, C. C., Scheiner, O., Jensen-Jarolim, E. (2007). Immunization with Mimotopes Prevents Growth of Carcinoembryonic Antigen Positive Tumors in BALB/c Mice. Clin. Cancer Res. 13: 6501-6508 [Abstract] [Full Text]  
• Kim, R., Emi, M., Tanabe, K., Arihiro, K. (2006). Tumor-Driven Evolution of Immunosuppressive Networks during Malignant Progression. Cancer Res. 66: 5527-5536 [Abstract] [Full Text]  
• Varga, Z., Theurillat, J.-P., Filonenko, V., Sasse, B., Odermatt, B., Jungbluth, A. A., Chen, Y.-T., Old, L. J., Knuth, A., Jager, D., Moch, H. (2006). Preferential Nuclear and Cytoplasmic NY-BR-1 Protein Expression in Primary Breast Cancer and Lymph Node Metastases.. Clin. Cancer Res. 12: 2745-2751 [Abstract] [Full Text]  
• Guo, Z. S., Hong, J. A., Irvine, K. R., Chen, G. A., Spiess, P. J., Liu, Y., Zeng, G., Wunderlich, J. R., Nguyen, D. M., Restifo, N. P., Schrump, D. S. (2006). De novo Induction of a Cancer/Testis Antigen by 5-Aza-2'-Deoxycytidine Augments Adoptive Immunotherapy in a Murine Tumor Model. Cancer Res. 66: 1105-1113 [Abstract] [Full Text]  
• Kloor, M., Becker, C., Benner, A., Woerner, S. M., Gebert, J., Ferrone, S., von Knebel Doeberitz, M. (2005). Immunoselective Pressure and Human Leukocyte Antigen Class I Antigen Machinery Defects in Microsatellite Unstable Colorectal Cancers. Cancer Res. 65: 6418-6424 [Abstract] [Full Text]  
• Sreekumar, A, Acharya, K K, Lalitha, H S, Indi, S S, Bali, P, Seshagiri, P B (2005). Germ cell-specific localization of immunoreactive riboflavin carrier protein in the male golden hamster: appearance during spermatogenesis and role in sperm function. Reproduction 129: 577-587 [Abstract] [Full Text]  
• Shang, X.-Y., Chen, H.-S., Zhang, H.-G., Pang, X.-W., Qiao, H., Peng, J.-R., Qin, L.-L., Fei, R., Mei, M.-H., Leng, X.-S., Gnjatic, S., Ritter, G., Simpson, A. J. G., Old, L. J., Chen, W.-F. (2004). The Spontaneous CD8+ T-Cell Response to HLA-A2-Restricted NY-ESO-1b Peptide in Hepatocellular Carcinoma Patients. Clin. Cancer Res. 10: 6946-6955 [Abstract] [Full Text]  
• Saff, R. R., Spanjaard, E. S., Hohlbaum, A. M., Marshak-Rothstein, A. (2004). Activation-Induced Cell Death Limits Effector Function of CD4 Tumor-Specific T Cells. J. Immunol. 172: 6598-6606 [Abstract] [Full Text]  
• Webb, A. I., Dunstone, M. A., Chen, W., Aguilar, M.-I., Chen, Q., Jackson, H., Chang, L., Kjer-Nielsen, L., Beddoe, T., McCluskey, J., Rossjohn, J., Purcell, A. W. (2004). Functional and Structural Characteristics of NY-ESO-1-related HLA A2-restricted Epitopes and the Design of a Novel Immunogenic Analogue. J. Biol. Chem. 279: 23438-23446 [Abstract] [Full Text]  
• Friedman, R. S., Bangur, C. S., Zasloff, E. J., Fan, L., Wang, T., Watanabe, Y., Kalos, M. (2004). Molecular and Immunological Evaluation of the Transcription Factor SOX-4 as a Lung Tumor Vaccine Antigen. J. Immunol. 172: 3319-3327 [Abstract] [Full Text]  
• Yamaguchi, H., Tanaka, F., Ohta, M., Inoue, H., Mori, M. (2004). Identification of HLA-A24-Restricted CTL Epitope from Cancer-Testis Antigen, NY-ESO-1, and Induction of a Specific Antitumor Immune Response. Clin. Cancer Res. 10: 890-896 [Abstract] [Full Text]  
• Palmowski, M. J., Lopes, L., Ikeda, Y., Salio, M., Cerundolo, V., Collins, M. K. (2004). Intravenous Injection of a Lentiviral Vector Encoding NY-ESO-1 Induces an Effective CTL Response. J. Immunol. 172: 1582-1587 [Abstract] [Full Text]  
• Flynn, S., Stockinger, B. (2003). Tumor and CD4 T-cell interactions: tumor escape as result of reciprocal inactivation. Blood 101: 4472-4478 [Abstract] [Full Text]  
• Zhu, B., Chen, Z., Cheng, X., Lin, Z., Guo, J., Jia, Z., Zou, L., Wang, Z., Hu, Y., Wang, D., Wu, Y. (2003). Identification of HLA-A*0201-restricted Cytotoxic T Lymphocyte Epitope from TRAG-3 Antigen. Clin. Cancer Res. 9: 1850-1857 [Abstract] [Full Text]  
• Davis, I. D., Jefford, M., Parente, P., Cebon, J. (2003). Rational approaches to human cancer immunotherapy. J. Leukoc. Biol. 73: 3-29 [Abstract] [Full Text]  
• Wang, L.-X., Chen, B.-G., Plautz, G. E. (2002). Adoptive Immunotherapy of Advanced Tumors with CD62 L-Selectinlow Tumor-Sensitized T Lymphocytes Following Ex Vivo Hyperexpansion. J. Immunol. 169: 3314-3320 [Abstract] [Full Text]  
• Dalgleish, A G (2001). Current problems in the development of specific immunotherapeutic approaches to cancer. J. Clin. Pathol. 54: 675-676 [Full Text]