A novel method for viral gene delivery in solid tumors.
Intratumoral infusion is the most commonly used method for viral gene delivery in clinical trials for cancer treatment. However, a potential problem in this approach is that viral vectors may disseminate from tumor to normal tissues during and after the infusion. To reduce the dissemination, we developed a novel method based on a biocompatible polymer, poloxamer 407, which could significantly increase the viscosity of virus suspension when the temperature was changed from 4 degrees C to 37 degrees C. With this method, we could significantly increase transgene expression in solid tumors and reduce virus dissemination by 2 orders of magnitude after intratumoral infusion of adenoviral vectors. The mechanism of reduction was likely to be that the viscous poloxamer solution blocked convection of viral vectors in the interstitial space and the lumen of microvessels in the vicinity of the infusion site. This method has a potential to be used in the clinic for enhancing efficacy and reducing toxicity in viral gene therapy.
Wang
Yong
Y
Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, USA.
Liu
Shanling
S
Li
Chuan-Yuan
CY
Yuan
Fan
F
D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000097:blood / Q000235:genetics* / Q000493:pharmacokinetics; D036502:Infusions, Intralesional; D008325:Mammary Neoplasms, Experimental / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D043942:Nanotubes; D020442:Poloxamer / Q000008:administration & dosage*; D019076:Transgenes
D020442:Poloxamer