TY - JOUR
T1 - Cells as vehicles for cancer gene therapy
T2 - The missing link between targeted vectors and systemic delivery?
AU - Harrington, Kevin
AU - Alvarez-Vallina, Luis
AU - Crittenden, Marka
AU - Gough, Michael
AU - Chong, Heung
AU - Diaz, Rosa Maria
AU - Vassaux, Georges
AU - Lemoine, Nicholas
AU - Vile, Richard
PY - 2002/7/20
Y1 - 2002/7/20
N2 - 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.
AB - 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.
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U2 - 10.1089/104303402760128504
DO - 10.1089/104303402760128504
M3 - Review article
C2 - 12162810
AN - SCOPUS:0036376654
SN - 1043-0342
VL - 13
SP - 1263
EP - 1280
JO - Human gene therapy
JF - Human gene therapy
IS - 11
ER -