Potent oncolytic activity of human enteroviruses against human prostate cancer.
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 compromised 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.


CONCLUSIONS
Enteroviruses CVA21, CVA21-DAFv, and EV1 are potentially potent oncolytic agents against human prostate cancer.
Berry
Linda J
LJ
The Picornavirus Research Unit, School of Biomedical Sciences, Faculty of Health, The University of Newcastle, Newcastle, New South Wales, Australia.
Au
Gough G
GG
Barry
Richard D
RD
Shafren
Darren R
DR
D000818:Animals; D018958:CD55 Antigens / Q000378:metabolism; D045744:Cell Line, Tumor; D029821:Enterovirus A, Human / Q000502:physiology*; D029822:Enterovirus B, Human / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D038982:Integrin alpha2beta1 / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D013047:Specific Pathogen-Free Organisms; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays
D018958:CD55 Antigens; D038982:Integrin alpha2beta1; D008562:Membrane Glycoproteins; D018799:Intercellular Adhesion Molecule-1