Enhanced central memory cluster of differentiation 8+ and tumor antigen-specific T cells in prostate cancer patients receiving repeated in situ adenovirus-mediated suicide gene therapy

Kubo,Makoto; Satoh,Takefumi; Tabata,Ken‑Ichi; Tsumura,Hideyasu; Iwamura,Masatsugu; Baba,Shiro; Thompson,Timothy  C.; Obata,Fumiya

doi:10.3892/mco.2015.519

Enhanced central memory cluster of differentiation 8+ and tumor antigen-specific T cells in prostate cancer patients receiving repeated in situ adenovirus-mediated suicide gene therapy

Authors:
- Makoto Kubo
- Takefumi Satoh
- Ken‑Ichi Tabata
- Hideyasu Tsumura
- Masatsugu Iwamura
- Shiro Baba
- Timothy C. Thompson
- Fumiya Obata
View Affiliations

Affiliations: Division of Immunology, Kitasato University School of Allied Health Sciences, Sagamihara, Kanagawa 252‑0373, Japan, Department of Urology, Kitasato University School of Medicine, Sagamihara, Kanagawa 252‑0373, Japan, Department of Genitourinary Medical Oncology, Research, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Published online on: February 26, 2015 https://doi.org/10.3892/mco.2015.519
Pages: 515-521
Copyright: © Kubo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The high relapse rate of prostate cancer following radical prostatectomy is clinically problematic, and various neoadjuvant therapies aimed at reducing the rate have been examined. A previous study has shown that immune responses are increased in patients treated by adenoviral vector‑mediated herpes simplex virus‑thymidine kinase (HSV‑tk) gene delivery followed by ganciclovir (GCV) injection. However, details of the immune responses following this form of gene therapy remain unclear. Five patients who agreed to participate in the present phase I/II trial were repeatedly administered GCV intravenously for 2 weeks following intraprostatic injection of HSV‑tk. Peripheral blood samples were periodically collected following the treatments, and lymphocyte subsets were analyzed by flow‑cytometry. Intracellular interferon (IFN)‑γ produced by T cells was further measured in response to prostatic acid phosphatase and NY‑ESO‑1 overlapping peptides. Central memory (CM) cluster of differentiation 8+ (CD8+) T cells were found to increase markedly during the second round of treatment. In three patients, tumor antigen‑specific T cells were clearly increased following HSV‑tk + GCV treatment. An increase in prostate cancer antigen‑specific T cells and CM CD8+ T cells may contribute to a reduction of relapse rates in prostate cancer patients receiving this form of gene therapy, which shows promise in a neoadjuvant setting.

View Figures

View References

1	Jones GW, Mettlin C, Murphy GP, et al: Patterns of care for carcinoma of the prostate gland: Results of a national survey of 1984 and 1990. J Am Coll Surg. 180:545–554. 1995.PubMed/NCBI
2	Center MM, Jemal A, Lortet-Tieulent J, Ward E, Ferlay J, Brawley O and Bray F: International variation in prostate cancer incidence and mortality rates. Eur Urol. 61:1079–1092. 2012. View Article : Google Scholar : PubMed/NCBI
3	Ohori M, Wheeler TM, Kattan MW, Goto Y and Scardino PT: Prognostic significance of positive surgical margins in radical prostatectomy specimens. J Urol. 154:1818–1824. 1995. View Article : Google Scholar : PubMed/NCBI
4	Zietman AL, Edelstein RA, Coen JJ, Babayan RK and Krane RJ: Radical prostatectomy for adenocarcinoma of the prostate: The influence of preoperative and pathologic findings on biochemical disease-free outcome. Urology. 43:828–833. 1994. View Article : Google Scholar : PubMed/NCBI
5	Namiki K and Rosser CJ: Neoadjuvant therapy and prostate cancer: What a urologist should know. Curr Opin Urol. 17:188–193. 2007. View Article : Google Scholar : PubMed/NCBI
6	Herman JR, Adler HL, Aguilar-Cordova E, Rojas-Martinez A, Woo S, Timme TL, Wheeler TM, Thompson TC and Scardino PT: In situ gene therapy for adenocarcinoma of the prostate: A phase I clinical trial. Hum Gene Ther. 10:1239–1249. 1999. View Article : Google Scholar : PubMed/NCBI
7	Shalev M, Kadmon D, Teh BS, Butler EB, Aguilar-Cordova E, Thompson TC, Herman JR, Adler HL, Scardino PT and Miles BJ: Suicide gene therapy toxicity after multiple and repeat injections in patients with localized prostate cancer. J Urol. 163:1747–1750. 2000. View Article : Google Scholar : PubMed/NCBI
8	Miles BJ, Shalev M, Aguilar-Cordova E, et al: Prostate-specific antigen response and systemic T cell activation after in situ gene therapy in prostate cancer patients failing radiotherapy. Hum Gene Ther. 12:1955–1967. 2001. View Article : Google Scholar : PubMed/NCBI
9	Thompson TC: In situ gene therapy for prostate cancer. Oncol Res. 11:1–8. 1999.PubMed/NCBI
10	Freeman SM, Abboud CN, Whartenby KA, Packman CH, Koeplin DS, Moolten FL and Abraham GN: The ‘bystander effect’: Tumor regression when a fraction of the tumor mass is genetically modified. Cancer Res. 53:5274–5283. 1993.PubMed/NCBI
11	Barba D, Hardin J, Sadelain M and Gage FH: Development of anti-tumor immunity following thymidine kinase-mediated killing of experimental brain tumors. Proc Natl Acad Sci USA. 91:4348–4352. 1994. View Article : Google Scholar : PubMed/NCBI
12	Gagandeep S, Brew R, Green B, Christmas SE, Klatzmann D, Poston GJ and Kinsella AR: Prodrug-activated gene therapy: Involvement of an immunological component in the ‘bystander effect’. Cancer Gene Ther. 3:83–88. 1996.PubMed/NCBI
13	Ayala G, Wheeler TM, Shalev M, Thompson TC, Miles B, Aguilar-Cordova E, Chakraborty S and Kadmon D: Cytopathic effect of in situ gene therapy in prostate cancer. Hum Pathol. 31:866–870. 2000. View Article : Google Scholar : PubMed/NCBI
14	Satoh T, Teh BS, Timme TL, et al: Enhanced systemic T-cell activation after in situ gene therapy with radiotherapy in prostate cancer patients. Int J Radiat Oncol Biol Phys. 59:562–571. 2004. View Article : Google Scholar : PubMed/NCBI
15	Hall SJ, Mutchnik SE, Chen SH, Woo SL and Thompson TC: Adenovirus-mediated herpes simplex virus thymidine kinase gene and ganciclovir therapy leads to systemic activity against spontaneous and induced metastasis in an orthotopic mouse model of prostate cancer. Int J Cancer. 70:183–187. 1997. View Article : Google Scholar : PubMed/NCBI
16	Hall SJ, Sanford MA, Atkinson G and Chen SH: Induction of potent antitumor natural killer cell activity by herpes simplex virus-thymidine kinase and ganciclovir therapy in an orthotopic mouse model of prostate cancer. Cancer Res. 58:3221–3225. 1998.PubMed/NCBI
17	Hassan W, Sanford MA, Woo SL, Chen SH and Hall SJ: Prospects for herpes-simplex-virus thymidine-kinase and cytokine gene transduction as immunomodulatory gene therapy for prostate cancer. World J Urol. 18:130–135. 2000. View Article : Google Scholar : PubMed/NCBI
18	Loimas S, Toppinen MR, Visakorpi T, Jänne J and Wahlfors J: Human prostate carcinoma cells as targets for herpes simplex virus thymidine kinase-mediated suicide gene therapy. Cancer Gene Ther. 8:137–144. 2001. View Article : Google Scholar : PubMed/NCBI
19	Vile RG, Castleden S, Marshall J, Camplejohn R, Upton C and Chong H: Generation of an anti-tumour immune response in a non-immunogenic tumour: HSVtk killing in vivo stimulates a mononuclear cell infiltrate and a Th1-like profile of intratumoural cytokine expression. Int J Cancer. 71:267–274. 1997. View Article : Google Scholar : PubMed/NCBI
20	Kianmanesh AR, Perrin H, Panis Y, Fabre M, Nagy HJ, Houssin D and Klatzmann D: A ‘distant’ bystander effect of suicide gene therapy: Regression of nontransduced tumors together with a distant transduced tumor. Hum Gene Ther. 8:1807–1814. 1997. View Article : Google Scholar : PubMed/NCBI
21	Whartenby KA, Abboud CN, Marrogi AJ, Ramesh R and Freeman SM: The biology of cancer gene therapy. Lab Invest. 72:131–145. 1995.PubMed/NCBI
22	Satoh T, Kubo M, Tabata K, et al: Systemic T-cell activation following neoadjuvant in situ gene therapy in high-risk prostate cancer patients. J Urol. 187:e3232012. View Article : Google Scholar
23	Ayala G, Satoh T, Li R, Shalev M, Gdor Y, Aguilarcordova E, Frolov A, Wheeler T, Miles B and Rauen K: Biological response determinants in HSV-tk + ganciclovir gene therapy for prostate cancer. Mol Ther. 13:716–728. 2006. View Article : Google Scholar : PubMed/NCBI
24	van der Linden RR, Haagmans BL, Mongiat-Artus P, van Doornum GJ, Kraaij R, Kadmon D, Aguilar-Cordova E, Osterhaus AD, van der Kwast TH and Bangma CH: Virus specific immune responses after human neoadjuvant adenovirus-mediated suicide gene therapy for prostate cancer. Eur Urol. 48:153–161. 2005. View Article : Google Scholar : PubMed/NCBI