Potent oncolytic activity of human enteroviruses against human prostate cancer

被引:40
作者
Berry, Linda J. [1 ]
Au, Gough G. [1 ]
Barry, Richard D. [1 ]
Shafren, Darren R. [1 ,2 ]
机构
[1] Univ Newcastle, Discipline Immunol & Microbiol, Picornavirus Res Unit, Fac Hlth,Sch Biomed Sci, Newcastle, NSW 2300, Australia
[2] Viralyt Ltd, Pymble Business Ctr, Pymble, NSW, Australia
关键词
virotherapy; enteroviruses; cellular receptors; xenograft; oncolysis;
D O I
10.1002/pros.20741
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 EVI are potentially potent oncolytic agents against human prostate cancer.
引用
收藏
页码:577 / 587
页数:11
相关论文
共 53 条
[1]   Gene expression of angiogenic factors correlates with metastatic potential of prostate cancer cells [J].
Aalinkeel, R ;
Nair, MPN ;
Sufrin, G ;
Mahajan, SA ;
Chadha, KC ;
Chawda, RP ;
Schwartz, SA .
CANCER RESEARCH, 2004, 64 (15) :5311-5321
[2]  
ASHKENAZI A, 1962, AM J CLIN PATHOL, V38, P209
[3]  
Au GG, 2005, INT J ONCOL, V26, P1471
[4]  
Bell J. C., 2002, Current Gene Therapy, V2, P243, DOI 10.2174/1566523024605582
[5]   Androgen responsive adult human prostatic epithelial cell lines immortalized by human papillomavirus 18 [J].
Bello, D ;
Webber, MM ;
Kleinman, HK ;
Wartinger, DD ;
Rhim, JS .
CARCINOGENESIS, 1997, 18 (06) :1215-1223
[6]   IDENTIFICATION OF THE INTEGRIN VLA-2 AS A RECEPTOR FOR ECHOVIRUS-1 [J].
BERGELSON, JM ;
SHEPLEY, MP ;
CHAN, BMC ;
HEMLER, ME ;
FINBERG, RW .
SCIENCE, 1992, 255 (5052) :1718-1720
[7]   DIFFERENTIAL EXPRESSION OF ALPHA-6 AND ALPHA-2 VERY LATE ANTIGEN INTEGRINS IN THE NORMAL, HYPERPLASTIC, AND NEOPLASTIC PROSTATE - SIMULTANEOUS DEMONSTRATION OF CELL-SURFACE RECEPTORS AND THEIR EXTRACELLULAR LIGANDS [J].
BONKHOFF, H ;
STEIN, U ;
REMBERGER, K .
HUMAN PATHOLOGY, 1993, 24 (03) :243-248
[8]   INTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1) HAS A CENTRAL ROLE IN CELL CELL CONTACT-MEDIATED IMMUNE-MECHANISMS [J].
BOYD, AW ;
WAWRYK, SO ;
BURNS, GF ;
FECONDO, JV .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (09) :3095-3099
[9]  
COYNE KE, 1992, J IMMUNOL, V149, P2906
[10]   Complement resistance of human carcinoma cells depends on membrane regulatory proteins, protein kinases and sialic acid [J].
Donin, N ;
Jurianz, K ;
Ziporen, L ;
Schultz, S ;
Kirschfink, M ;
Fishelson, Z .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2003, 131 (02) :254-263