scholarly journals Intra-arterial Delivery of a Recombinant Adenovirus Does Not Increase Gene Transfer to Tumor Cells in a Rat Model of Metastatic Colorectal Carcinoma

2001 ◽  
Vol 4 (1) ◽  
pp. 29-35 ◽  
Author(s):  
David J. Maron ◽  
Hiroomi Tada ◽  
A.David Moscioni ◽  
John Tazelaar ◽  
Douglas L. Fraker ◽  
...  
1996 ◽  
Vol 85 (4) ◽  
pp. 648-654 ◽  
Author(s):  
Arnaud J. P. E. Vincent ◽  
Maria del C. Esandi ◽  
Gerry van Someren ◽  
Juus L. Noteboom ◽  
Cees J. J. Avezaat ◽  
...  

✓ The authors constructed recombinant adenoviral vectors to investigate their potential for gene therapy treatment of leptomeningeal metastases. Several human cell lines that were derived from tumors occurring as leptomeningeal metastases and that were infected in vitro with major late promoter recombinant adenovirus containing the luciferase (luc) gene (IG.Ad.MLP.luc.) showed high levels of expression. When these human tumor cell lines were infected in vitro with recombinant adenovirus harboring the herpes simplex virus—thymidine kinase (HSV-tk) gene (IG.Ad.MLP.TK), they were highly sensitive to the killing effects of ganciclovir (GCV). Transduction efficiency of leptomeningeal tumor cells in vivo was assessed by injecting 9-L rat brain tumor cells into the cerebrospinal fluid of Fischer rats via the cisterna magna. After 3 days, recombinant adenovirus containing the lacZ reporter gene (IG.Ad.MLP.lacZ) was injected via the same route. Six days after tumor cell injection, expression of the reporter gene was observed in tumor cells along the total neural axis. Subsequently, rats with leptomeningeal metastases were treated 3 days after tumor cell injection with HSV-tk. Beginning on the next day, GCV was injected intraperitoneally for 10 days. The rats that developed neurological symptoms were killed immediately. The symptom-free latency of every rat was determined. The rats treated with HSV-tk and subsequent GCV had significantly longer (p < 0.01) symptom-free latency than all control groups. This study demonstrates the feasibility and efficacy of this therapeutic approach in a rat model. Clinically, it should be used in the palliative treatment of patients with leptomeningeal metastases.


2004 ◽  
Vol 29 (8) ◽  
pp. 485-487 ◽  
Author(s):  
Phivi Rondogianni ◽  
George Koniaris

1990 ◽  
Vol 172 (4) ◽  
pp. 1217-1224 ◽  
Author(s):  
B Gansbacher ◽  
K Zier ◽  
B Daniels ◽  
K Cronin ◽  
R Bannerji ◽  
...  

To study the effects of localized secretion of cytokines on tumor progression, the gene for human interleukin 2 (IL-2) was introduced via retroviral vectors into CMS-5 cells, a weakly immunogenic mouse fibrosarcoma cell line of BALB/c origin. Secretion of low levels of IL-2 from the tumor cells abrogated their tumorigenicity and induced a long-lasting protective immune response against a challenge with a tumorigenic dose of parental CMS-5 cells. Co-injection of IL-2-producing CMS-5 cells with unmodified tumor cells inhibited tumor formation even when highly tumorigenic doses of CMS-5 cells were used. Cytolytic activity in mice injected with parental CMS-5 cells was transient and was greatly diminished 3 wk after injection, as commonly observed in tumor-bearing animals. However, in mice injected with IL-2-producing cells, tumor-specific cytolytic activity persisted at high levels for the duration of the observation period (at least 75 d). High levels of tumor-specific cytolytic activity could also be detected in parental CMS-5 tumor-bearing animals 18 d after inoculation with tumor cells, if IL-2-producing CMS-5 cells but not unmodified parental tumor cells were used as targets. These studies highlight the potential advantages of localized secretion of cytokines mediated via gene transfer to induce potent anti-tumor immune responses.


HPB ◽  
2010 ◽  
Vol 12 (1) ◽  
pp. 31-36 ◽  
Author(s):  
Matthew Bower ◽  
Tiffany Metzger ◽  
Ken Robbins ◽  
Dana Tomalty ◽  
Vlatimil Válek ◽  
...  

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