Original Article

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

  1. Maurizio Chiriva-Internati1,2,*,
  2. Yuefei Yu1,
  3. Leonardo Mirandola1,
  4. Nicholas D'Cunha1,
  5. Fred Hardwicke1,
  6. Martin J. Cannon3,
  7. Everardo Cobos1,
  8. W. Martin Kast2,4,5

Article first published online: 25 APR 2011

DOI: 10.1002/pros.21400

Issue

The Prostate

The Prostate

Volume 72, Issue 1, pages 12–23, January 2012

Additional Information

How to Cite

Chiriva-Internati, M., Yu, Y., Mirandola, L., D'Cunha, N., Hardwicke, F., Cannon, M. J., Cobos, E. and Kast, W. M. (2012), Identification of AKAP-4 as a new cancer/testis antigen for detection and immunotherapy of prostate cancer. Prostate, 72: 12–23. doi: 10.1002/pros.21400

Author Information

  1. 1

    Division of Hematology & Oncology, Texas Tech University Health Sciences Center and The Southwest Cancer Treatment and Research Center, Lubbock, Texas

  2. 2

    Kiromic, Inc., Lubbock, Texas

  3. 3

    Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas

  4. 4

    Departments of Molecular Microbiology & Immunology, Obstetrics & Gynaecology and Urology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California

  5. 5

    Cancer Research Center of Hawaii, University of Hawaii at Manoa, Honolulu, Hawaii

*Division of Hematology & Oncology, Texas Tech University Health Sciences Center, 3601 4th St., Mail Stop 9410, Lubbock, TX 79430.

  1. †

    Conflict of interest disclosure: the authors have no conflict of interest to disclose.

Publication History

  1. Issue published online: 24 NOV 2011
  2. Article first published online: 25 APR 2011
  3. Manuscript Accepted: 16 MAR 2011
  4. Manuscript Received: 27 OCT 2010

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Keywords:

  • prostate cancer;
  • biomarkers;
  • cancer/testis antigens;
  • AKAP;
  • immunotherapy;
  • immune surveillance

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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