NY‐ESO‐1: Review of an Immunogenic Tumor Antigen

https://doi.org/10.1016/S0065-230X(06)95001-5Get rights and content

In the 9 years since its discovery, cancer‐testis antigen NY‐ESO‐1 has made one of the fastest transitions from molecular, cellular, and immunological description to vaccine and immunotherapy candidate, already tested in various formulations in more than 30 clinical trials worldwide. Its main characteristic resides in its capacity to elicit spontaneous antibody and T‐cell responses in a proportion of cancer patients. An overview of immunological findings and immunotherapeutic approaches with NY‐ESO‐1, as well the role of regulation in NY‐ESO‐1 immunogenicity, is presented here.

Section snippets

Name and Family History

The etymology of NY‐ESO‐1 tells the story of its origins: NY stands for the city in which it was discovered by Chen et al. (1997), at the Ludwig Institute for Cancer Research and Weill Medical College of Cornell University in New York, in 1997; ESO is for esophageal cancer where it was originally described by screening a tumor‐derived cDNA expression library with autologous serum of an esophageal cancer patient; and this was the first member of a new gene family.

The gene coding for NY‐ESO‐1,

Indications and Usage: Expression of NY‐ESO‐1 in Tumor Cells

The promise of NY‐ESO‐1 as a candidate for specific immune recognition of cancer comes from its restricted expression in normal tissues but frequent occurrence in cancer. Although originally described from the cDNA sequences of an esophageal tumor, NY‐ESO‐1 has shown a much more widespread incidence in a number of other tumor types. The expression of NY‐ESO‐1 has been analyzed in surgically removed primary or metastatic cancer tissues on two levels: message by RT‐PCR and protein by

Concluding Remarks

Knowing what to expect is not a luxury when planning immunotherapeutic intervention, and NY‐ESO‐1 with its strong inherent immunogenicity in a subset of cancer patients has set the standards to reach. With a booming number of clinical trials with NY‐ESO‐1 as a model antigen, clinical correlations of immunogenicity and patient benefit, if any, should soon be established. Current vaccines still have a lot of room for improvement, both in antigen and in adjuvant formulations. An efficient vaccine

Acknowledgments

We are grateful to Ramon Chua and Bernadette Keitz for their help in generating and compiling the RT‐PCR data.

Financial Support: Supported by the Cancer Vaccine Collaborative funded by the Cancer Research Institute and Ludwig Institute for Cancer Research.

References (109)

  • H.Y. Wang et al.

    Tumor‐specific human CD4+ regulatory T cells and their ligands: Implications for immunotherapy

    Immunity

    (2004)
  • C.A. Aarnoudse et al.

    Interleukin‐2‐induced, melanoma‐specific T cells recognize CAMEL, an unexpected translation product of LAGE‐1

    Int. J. Cancer

    (1999)
  • A. Akcakanat et al.

    NY‐ESO‐1 expression and its serum immunoreactivity in esophageal cancer

    Cancer Chemother. Pharmacol.

    (2004)
  • M.L. Albert et al.

    Dendritic cells acquire antigen from apoptotic cells and induce class I‐restricted CTLs

    Nature

    (1998)
  • M. Ayyoub et al.

    The frequent expression of cancer/testis antigens provides opportunities for immunotherapeutic targeting of sarcoma

    Cancer Immun.

    (2004)
  • H. Benlalam et al.

    Comprehensive analysis of the frequency of recognition of melanoma‐associated antigen (MAA) by CD8 melanoma infiltrating lymphocytes (TIL): Implications for immunotherapy

    Eur. J. Immunol.

    (2001)
  • S.J. Bensinger et al.

    Major histocompatibility complex class II‐positive cortical epithelium mediates the selection of CD4(+)25(+) immunoregulatory T cells

    J. Exp. Med.

    (2001)
  • M. Bolli et al.

    NY‐ESO‐1/LAGE‐1 coexpression with MAGE‐A cancer/testis antigens: A tissue microarray study

    Int. J. Cancer

    (2005)
  • H.S. Chen et al.

    Expression of tumor‐specific cancer/testis antigens in hepatocellular carcinoma

    Zhonghua Gan Zang Bing Za Zhi

    (2003)
  • J.‐L. Chen et al.

    Identification of NY‐ESO‐1 peptide analogues capable of improved stimulation of tumor‐reactive CTL

    J. Immunol.

    (2000)
  • J.‐L. Chen et al.

    Structural and kinetic basis for heightened immunogenicity of T cell vaccines

    J. Exp. Med.

    (2005)
  • Q. Chen et al.

    Immunodominant CD4+ responses identified in a patient vaccinated with full‐length NY‐ESO‐1 formulated with ISCOMATRIX adjuvant

    Proc. Natl. Acad. Sci. USA

    (2004)
  • Q. Chen et al.

    Characterization of antigen‐specific CD8+ T lymphocyte responses in skin and peripheral blood following intradermal peptide vaccination

    Cancer Immun.

    (2005)
  • Y.‐T. Chen et al.

    A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening

    Proc. Natl. Acad. Sci. USA

    (1997)
  • Z.M. Cilensek et al.

    A member of the GAGE family of tumor antigens is an anti‐apoptotic gene that confers resistance to Fas/CD95/APO‐1, interferon‐gamma, taxol and gamma‐irradiation

    Cancer Biol. Ther.

    (2002)
  • N.A. Danke et al.

    Autoreactive T cells in healthy individuals

    J. Immunol.

    (2004)
  • I.D. Davis et al.

    Recombinant NY‐ESO‐1 protein with ISCOMATRIX adjuvant induces broad integrated antibody and CD4(+) and CD8(+) T cell responses in humans

    Proc. Natl. Acad. Sci. USA

    (2004)
  • C. De Smet et al.

    The activation of human gene MAGE‐1 in tumor cells is correlated with genome‐wide demethylation

    Proc. Natl. Acad. Sci. USA

    (1996)
  • M.V. Dhodapkar et al.

    Expression of cancer/testis (CT) antigens MAGE‐A1, MAGE‐A3, MAGE‐A4, CT‐7, and NY‐ESO‐1 in malignant gammopathies is heterogeneous and correlates with site, stage and risk status of disease

    Cancer Immun.

    (2003)
  • V. Dutoit et al.

    Functional avidity of tumor antigen‐specific CTL recognition directly correlates with the stability of MHC/peptide multimer binding to TCR

    J. Immunol.

    (2002)
  • V. Dutoit et al.

    Multiepitope CD8(+) T cell response to a NY‐ESO‐1 peptide vaccine results in imprecise tumor targeting

    J. Clin. Invest.

    (2002)
  • A. Fossa et al.

    NY‐ESO‐1 protein expression and humoral immune responses in prostate cancer

    Prostate

    (2004)
  • S. Fujita et al.

    NY‐ESO‐1 expression and immunogenicity in esophageal cancer

    Clin. Cancer Res.

    (2004)
  • B. Gaugler et al.

    Human gene MAGE‐3 codes for an antigen recognized on a melanoma by autologous cytolytic T lymphocytes

    J. Exp. Med.

    (1994)
  • S. Gnjatic et al.

    Strategy for monitoring T cell responses to NY‐ESO‐1 in patients with any HLA class I allele

    Proc. Natl. Acad. Sci. USA

    (2000)
  • S. Gnjatic et al.

    CD8+ T cell responses against a dominant cryptic HLA‐A2 epitope after NY‐ESO‐1 peptide immunization of cancer patients

    Proc. Natl. Acad. Sci. USA

    (2002)
  • S. Gnjatic et al.

    Survey of naturally occurring CD4+ T cell responses against NY‐ESO‐1 in cancer patients: Correlation with antibody responses

    Proc. Natl. Acad. Sci. USA

    (2003)
  • S. Gnjatic et al.

    Cross‐presentation of HLA class I epitopes from exogenous NY‐ESO‐1 polypeptides by nonprofessional APCs

    J. Immunol.

    (2003)
  • J. Gotter et al.

    Medullary epithelial cells of the human thymus express a highly diverse selection of tissue‐specific genes colocalized in chromosomal clusters

    J. Exp. Med.

    (2004)
  • A.O. Güre et al.

    Cancer‐testis genes are coordinately expressed and are markers of poor outcome in non‐small cell lung cancer

    Clin. Cancer Res.

    (2005)
  • E. Huarte et al.

    HLA‐DP4 expression and immunity to NY‐ESO‐1: Correlation and characterization of cytotoxic CD4+ CD25‐ CD8‐ T cell clones

    Cancer Immun.

    (2004)
  • K. Hung et al.

    The central role of CD4(+) T cells in the antitumor immune response

    J. Exp. Med.

    (1998)
  • M.S. Jordan et al.

    Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self‐peptide

    Nat. Immunol.

    (2001)
  • A.A. Jungbluth et al.

    Monophasic and biphasic synovial sarcomas abundantly express cancer/testis antigen NY‐ESO‐1 but not MAGE‐A1 or CT7

    Int. J. Cancer

    (2001)
  • A.A. Jungbluth et al.

    Meeting abstract

    Mod. Pathol.

    (2001)
  • A.A. Jungbluth et al.

    Immunohistochemical analysis of NY‐ESO‐1 antigen expression in normal and malignant human tissues

    Int. J. Cancer

    (2001)
  • A.A. Jungbluth et al.

    Meeting abstract

    Pathol. Res. Pract.

    (2001)
  • D. Jäger et al.

    Urine antibody against human cancer antigen NY‐ESO‐1

    Cancer Immun.

    (2002)
  • E. Jäger et al.

    Simultaneous humoral and cellular immune response against cancer‐testis antigen NY‐ESO‐1: Definition of human histocompatibility leukocyte antigen (HLA)‐A2‐binding peptide epitopes

    J. Exp. Med.

    (1998)
  • E. Jäger et al.

    Humoral immune responses of cancer patients against “Cancer‐Testis” antigen NY‐ESO‐1: Correlation with clinical events

    Int. J. Cancer

    (1999)
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