Identification of AKAP-4 as a new cancer/testis antigen for detection and immunotherapy of prostate cancer

Authors

  • Maurizio Chiriva-Internati,

    Corresponding author
    1. Division of Hematology & Oncology, Texas Tech University Health Sciences Center and The Southwest Cancer Treatment and Research Center, Lubbock, Texas
    2. Kiromic, Inc., Lubbock, Texas
    • Division of Hematology & Oncology, Texas Tech University Health Sciences Center, 3601 4th St., Mail Stop 9410, Lubbock, TX 79430.
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  • Yuefei Yu,

    1. Division of Hematology & Oncology, Texas Tech University Health Sciences Center and The Southwest Cancer Treatment and Research Center, Lubbock, Texas
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  • Leonardo Mirandola,

    1. Division of Hematology & Oncology, Texas Tech University Health Sciences Center and The Southwest Cancer Treatment and Research Center, Lubbock, Texas
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  • Nicholas D'Cunha,

    1. Division of Hematology & Oncology, Texas Tech University Health Sciences Center and The Southwest Cancer Treatment and Research Center, Lubbock, Texas
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  • Fred Hardwicke,

    1. Division of Hematology & Oncology, Texas Tech University Health Sciences Center and The Southwest Cancer Treatment and Research Center, Lubbock, Texas
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  • Martin J. Cannon,

    1. Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas
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  • Everardo Cobos,

    1. Division of Hematology & Oncology, Texas Tech University Health Sciences Center and The Southwest Cancer Treatment and Research Center, Lubbock, Texas
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  • W. Martin Kast

    1. Kiromic, Inc., Lubbock, Texas
    2. Departments of Molecular Microbiology & Immunology, Obstetrics & Gynaecology and Urology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California
    3. Cancer Research Center of Hawaii, University of Hawaii at Manoa, Honolulu, Hawaii
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  • Conflict of interest disclosure: the authors have no conflict of interest to disclose.

Abstract

BACKGROUND

Prostate cancer (PC) is the second most common cancer in older men, after skin cancer. PC is difficult to diagnose because the prostate-specific antigen screening method is associated with many false positives. In addition there is a need to develop new and more effective treatments. Among presently available new treatments, immunotherapy is a promising approach. We investigated the expression of the cancer/testis antigen, AKAP-4, in PC patients to evaluate the possibility of exploiting AKAP-4 as a target for immunotherapy.

METHODS

We analyzed normal prostate tissues, 15 patients with PC and the LnCAP PC cell line by immunohistochemistry. We tested AKAP-4 immunogenicity through indirect ELISA on sera from patients and healthy subjects, and we generated in vitro AKAP-4-specific cytotoxic lymphocytes from peripheral blood mononuclear cells.

RESULTS

AKAP-4 was shown both at the cytoplasmic and surface levels of the LnCAP PC cell line. AKAP-4 was also highly expressed in PC cells from patients. We detected specific anti-AKAP-4 circulating immunoglobulins in AKAP-4 positive subjects. Using recombinant AKAP-4 loaded autologous dendritic cells, we generated AKAP-4-specific and HLA-I-restricted cytotoxic T lymphocytes able to kill PC cells in vitro. Further characterization indicated a Th-1 skewing in the cytokine secretion profile of these cells.

CONCLUSIONS

We demonstrate the aberrant expression of AKAP-4 in PC, which will potentially be developed as a biomarker in PC. We provide evidence that AKAP-4 is a potential target for PC adoptive immunotherapy or anti-tumor vaccination. Prostate 72:12–23, 2012. © 2011 Wiley Periodicals, Inc.

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