Cells as vehicles for cancer gene therapy: the missing link between targeted vectors and systemic delivery?
Systemic administration of currently manufactured viral stocks has not so far achieved sufficient circulating titers to allow therapeutic targeting of metastatic disease. This is due to low initial viral titers, immune inactivation, nonspecific adhesion, and loss of particles. One way to exploit the elegant molecular manipulations that have been made to increase vector targeting is to protect these vectors until they reach the local sites of tumor growth. Various cell types home preferentially to tumors and can be loaded with the constructs required to produce targeted vectors. Here we discuss the potential of using such cell carriers to chaperone precious vectors directly to the tumors. The vectors can incorporate mechanisms to achieve tumor site-inducible expression, along with tumor cell-specific expression of the therapeutic gene and/or replicating viral genomes that would be released at the tumor. In this way, the great advances that have so far been made with the engineering of vector tropisms might be genuinely exploited and converted into clinical benefit.
Harrington
Kevin
K
Cancer Research Campaign, Centre for Cell and Molecular Biology, Chester Beatty Laboratories, Institute of Cancer Research, London SW3 6JB, UK.
Alvarez-Vallina
Luis
L
Crittenden
Marka
M
Gough
Michael
M
Chong
Heung
H
Diaz
Rosa Maria
RM
Vassaux
Georges
G
Lemoine
Nicholas
N
Vile
Richard
R
D017690:Cell Transplantation; D016503:Drug Delivery Systems / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D018390:Gene Targeting; D018014:Gene Transfer Techniques; D005818:Genetic Engineering / Q000379:methods; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000628:therapy*; D012190:Retroviridae / Q000235:genetics; D014777:Virus Diseases / Q000235:genetics / Q000628:therapy