Oncolytic viruses for cancer treatment

Transcription

1 Journal of Microbes and Infection, March 2009, Vol. 4, No. 1 35,, :,, : ; ; Oncolytic viruses for cancer treatment HOU Jian-Gang, DING Qiang Department of Urology, Huashan Hospital, Fudan University, Shanghai , China Abstract: Tremendous advances have been made in developing oncolytic viruses in the last few years. Viral infection and amplification eventually induce cancer cells into cell death pathways and elicit host antitumor immune responses. Specifically targeted molecules or signaling pathways in cancer cells or in the tumor microenvironment have been studied and a variety of oncolytic viruses such as adenovirus, herpes simplex virus, poxvirus, measles virus, Newcastle disease virus and influenza virus have been identified. In this review, the characteristics of oncolytic viruses for cancer therapy are discussed. Key words: Oncolytic virus; Gene recombinant; Tumor therapy,,, 100%, ( ) ( ),,,,, 100,,, 2 3 :, hou_jiangang@ hotmail. com Corresponding author: HOU Jian-Gang, hou_jiangang@ hotmail. com 1,,,,, ( ),,,, ;,,,,,,,, [ 1 ]

2 Journal of Microbes and Infection, March 2009, Vol. 4, No. 1,,,, DNA,,, , 1, 1911, 1,,, 20 50,, 20 70,, Burkitt Hodgkin,,,, 1991 Martuza [ 2] 1 ( herpes simplex virus type 1, HSV-1),,, HSV-1,, , : ;,, 9, ras, pfu, 11%,,,,, ras, PV701 HUJ PV701, , 12 h, [ 3] 11 HUJ, 1 3,,,, [ 4] HSV-1, HF10 6, [ 5, 6 ] 3. 2,,,, ,,,, HSV HSV-1 :, ( multiplicity of infection, MOI) ;, HSV-1

3 Journal of Microbes and Infection, March 2009, Vol. 4, No [ 7] ; HSV-1,,, ;, HSV-1 DNA ; HSV-1 ( 152 kb),,, HSV-1 G NV1020 OncoVEX GM-CSF, 34. 5, R( protein kinase R, PKR), HSV-1 PKR, ; PKR, 1 1,, 2 G207 G , lacz, ICP6 [ 8 ] G207 [ 9], G207 ( ) HSV-1 ( Aotusnancymae), pfu F, 5 d ; pfu G207, [ 10, 11 ] G207, G pfu,, ( magnetic resonance imaging, MRI) 4 30 d 20, 8, 2 5, [ 12], G G47 G47G207,, HSV-1 [ 13] 47,, G47, G207 [ 14] HSV-1,, pfu,,, [ 1 5] 1, G207, NV 1020( R7020),, NV1020, 34. 5, HSV-2 NV1020,, pfu [ 16],, NV 1020, / 47 HSV-1 - ( granulocytemacrophage colony stimulating factor, GM-CSF) OncoVEX GM-CSF, [ 17 ],,,,,, OncoVEX GM-CSF, HSV :, pfu; 36 kb,, ; HSV, DNA :, ;, MOI(

4 Journal of Microbes and Infection, March 2009, Vol. 4, No. 1 HSV-1, HSV ) ;, ONYX-015( d11520), 1987 Barker Berk 1996, Bischoff [ 1 8] p53 E1B 55kD,, p53,,, p53,, ONYX-015,,,,,, 10 d DNA,, 14%, [ 1 9], 5-Fu, 30%, 65% [ 20 ] H101 5, ONYX-015,, [ 21, 22 ],,, CG7060 CN706 ( prostate specific antigen, PSA) [ 2 3] CG7870 CN787 CN787 probasin PSA Ad5E1B CG7060 CG7870, 23 CG7870, PSA ; 2 3, Ad5-CD/TKrep E1B 2, [ 24 ],,,, ONYX-015 H101 E3,,,,, JX-594 tk, GM-CSF, Mastrangelo [ 25 ] 31 7 JX-594,, 5 ( 71% ), 1 GS-CSF mrna, T B, GM- CSF 7, 4 Park [ 26 ] 14,, 3 ( 3. 4 ), 1 3 ; ; 2 ( pfu), ; 10, 1, 3, 6 JX MV-CEA CEA [ 27 ] CD46, 4 HSV-1,,,, 500,

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