Conflict of interest disclosure: the authors have no conflict of interest to disclose.
Identification of AKAP-4 as a new cancer/testis antigen for detection and immunotherapy of prostate cancer†
Article first published online: 25 APR 2011
Copyright © 2011 Wiley Periodicals, Inc.
Volume 72, Issue 1, pages 12–23, January 2012
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
- Issue published online: 24 NOV 2011
- Article first published online: 25 APR 2011
- Manuscript Accepted: 16 MAR 2011
- Manuscript Received: 27 OCT 2010
- prostate cancer;
- cancer/testis antigens;
- immune surveillance
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.
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.
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.
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.