Tissue-specific promoters for cancer gene therapy.
Adenoviral cancer gene therapy approaches have resulted in promising recent results. Following only a decade of intense development, some of the crucial obstacles are now being overcome. Insufficient transduction has been the main limitation of earlier approaches. A new approach for increasing transduction of tumour cells is utilisation of replication-competent oncolytic agents, such as conditionally replicating adenoviruses (CRADs). The anti-tumour effect is caused by replication of the virus per se and, thus, replication must be restricted to tumour cells to protect normal tissues from damage. Tissue-specific promoters (TSPs) represent a powerful tool for decreasing the toxicity of cancer gene therapy to normal tissues and have previously been utilised for specific mutation compensation or delivery of prodrug-converting enzymes. However, TSPs can also be used for controlling crucial viral replication regulators and consequent restriction of replication to tumour cells. Initial clinical trials have demonstrated the safety and suggested efficacy for TSP-controlled CRADs as a novel approach for cancer gene therapy.
Saukkonen
Kirsi
K
Cancer Gene Therapy Group, Rational Drug Design, Biomedicum Helsinki, Department of Oncology, Helsinki University Central Hospital, University of Helsinki, Finland.
Hemminki
Akseli
A
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002986:Clinical Trials as Topic; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D018390:Gene Targeting; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D009369:Neoplasms / Q000628:therapy*; D011401:Promoter Regions, Genetic / Q000235:genetics*