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Potent Oncolytic activity of human enteroviruses against human prostate cancer
Author(s) -
Berry Linda J.,
Au Gough G.,
Barry Richard D.,
Shafren Darren R.
Publication year - 2008
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20741
Subject(s) - oncolytic virus , prostate cancer , prostate , medicine , cancer , cancer research , oncology , biology
BACKGROUND Oncolytic virotherapy offers a unique treatment modality for prostate cancer, especially stages that are resistant to current therapies, with the additional benefit of preferentially targeting tumor cells amongst an environment of healthy tissue. Herein, the low pathogenic enteroviruses; Coxsackievirus A21 (CVA21), as well as a bio‐selected variant of Coxsackievirus A21 (CVA21‐DAFv) and Echovirus 1 (EV1) are evaluated as novel oncolytic agents against human prostate cancer. METHODS The surface expression of viral receptors required for enterovirus cell attachment/entry, including intercellular adhesion molecule‐1 (ICAM‐1), decay‐accelerating factor (DAF) and integrin alpha 2 beta 1 on a number of human prostate cancer lines was assessed by flow cytometry. Susceptibility to viral oncolysis was determined via in vitro cell lysis assays performed on cell monolayers cultured in micro titer plates. The in vivo oncolytic efficacy of the enteroviruses was assessed using xenograft models in immune compromized SCID‐mice following systemic challenge. RESULTS The majority of prostate cancer lines tested expressed surface ICAM‐1 and/or DAF, or alpha 2 beta 1 , facilitating significant degrees of oncolysis following in vitro viral challenge. Systemic delivery of each of the three viruses induced reduction of xenograft tumor burdens in vivo, and a therapeutic dose‐response was demonstrated for escalating doses of EV1 in the LNCaP animal model. CONCLUSION Enteroviruses CVA21, CVA21‐DAFv, and EV1 are potentially potent oncolytic agents against human prostate cancer. Prostate 68: 577–587, 2008. © 2008 Wiley‐Liss, Inc.