Oncolytic virotherapy for cancer with the adenovirus dl1520 (Onyx-015):: results of Phase I and II trials

被引:130
作者
Kirn, D [1 ]
机构
[1] Hammersmith Hosp, Mol Oncol Unit, Imperial Canc Res Fund, Viral & Genet Therapy Programme, London, England
关键词
adenovirus; cancer; clinical research; gene therapy; viral therapy;
D O I
10.1517/14712598.1.3.525
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Replication-selective viral agents hold promise as a novel cancer treatment platform (virotherapy). dl1520 (Onyx-015, now CI-1042, Pfizer Corp., Groton, CT, USA), an E1B-55kD gene-deleted adenovirus, was the first such genetically engineered agent to be tested in humans. Over 250 cancer patients have now been treated on approximately ten clinical trials (phase I-III). The virus was generally well tolerated at doses of up to 2 x 10(12) particles by intratumoural, intraperitoneal, hepatic arterial and iv. administration; no maximally-tolerated doses were identified following intra-vascular administration. Viral replication was tumour-selective and was documented after administration by all routes; however, viral replication was variable depending on tumour histology. Single agent efficacy has been relatively limited to date (0 - 14% local tumour regression rates). In combination with chemotherapy, however, encouraging antitumoural activity has been demonstrated. These clinical research results demonstrate the potential of this novel treatment platform, as well as the hurdles to be overcome. Novel replication-selective agents with improved potency are being developed.
引用
收藏
页码:525 / 538
页数:14
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