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New gene expressed in prostate: a potential target for T cell-mediated prostate cancer immunotherapy

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Abstract

New gene expressed in prostate (NGEP) is a prostate-specific gene encoding either a small cytoplasmic protein (NGEP-S) or a larger polytopic membrane protein (NGEP-L). NGEP-L expression is detectable only in prostate cancer, benign prostatic hyperplasia and normal prostate. We have identified an HLA-A2 binding NGEP epitope (designated P703) which was used to generate T cell lines from several patients with localized and metastatic prostate cancer. These T cell lines were able to specifically lyse HLA-A2 and NGEP-expressing human tumor cells. NGEP-P703 tetramer binding assays demonstrated that metastatic prostate cancer patients had a higher frequency of NGEP-specific T cells when compared with healthy donors. Moreover, an increased frequency of NGEP-specific T cells was detected in the peripheral blood mononuclear cells of prostate cancer patients post-vaccination with a PSA-based vaccine, further indicating the immunogenicity of NGEP. These studies thus identify NGEP as a potential target for T cell-mediated immunotherapy of prostate cancer.

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Abbreviations

APC:

Antigen-presenting cells

CTL:

Cytotoxic T lymphocytes

DC:

Dendritic cells

EBV:

Epstein Barr virus

EST:

Expressed sequence tag

E:T:

Effector:target

HLA-A2:

Human leukocyte antigen-A2 allele

IFN:

Interferon

IVS:

In vitro stimulation

mAb:

Monoclonal antibody

MFI:

Mean fluorescence intensity

NGEP:

New gene expressed in prostate

PBMC:

Peripheral blood mononuclear cells

PE:

Phycoerythrin

PSA:

Prostate-specific antigen

TRICOM:

Triad of costimulatory molecules (B7.1, ICAM-1, LFA-3)

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Acknowledgments

The authors thank Bonnie Casey and Debra Weingarten for their editorial assistance in the preparation of this manuscript. This research was supported by the Intramural Research Program of the Center for Cancer Research, NCI, NIH.

Conflict of interest statement

There are no potential conflicts of interest.

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Authors and Affiliations

  1. Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Room 8B09, Bethesda, MD, 20892, USA

    Vittore Cereda, Diane J. Poole, Claudia Palena, Cinzia Remondo, James L. Gulley, Philip M. Arlen, Junko Yokokawa, Jeffrey Schlom & Kwong Y. Tsang

  2. Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Room 5106, Bethesda, MD, USA

    Sudipto Das, Tapan K. Bera & Ira Pastan

Authors
  1. Vittore Cereda
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  2. Diane J. Poole
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  3. Claudia Palena
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  4. Sudipto Das
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Correspondence to Jeffrey Schlom.

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Cereda, V., Poole, D.J., Palena, C. et al. New gene expressed in prostate: a potential target for T cell-mediated prostate cancer immunotherapy. Cancer Immunol Immunother 59, 63–71 (2010). https://doi.org/10.1007/s00262-009-0723-6

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  • DOI: https://doi.org/10.1007/s00262-009-0723-6

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