Infectious Retrovirus Is Inactivated by Serum but Not by Cerebrospinal Fluid or Fluid from Tumor Bed in Patients with Malignant Glioma

Abstract

Intravenous gene transfer using recombinant retroviruses tends to suffer from a low infectious viral titer when conducted in vivo. This is, in part, caused by complement‐mediated proteolytic inactivation of the retrovirus in human serum. However, if the retroviruses were directly injected into the brain, they might not be inactivated. Supernatant from amphotropic retrovirus‐producing cells harboring the BAG vectors was incubated with sera or cerebrospinal fluid (CSF) of patients with gliomas or unrelated disorders. The retroviruses were severely inactivated in sera. However, no such inactivation was noted in CSF or fluid from the tumor bed of glioma patients. These data suggest that gene transfer using recombinant retroviruses could be done into the cavity after removal of the tumor in glioma patients.

Clinical-Scale Selection of Anti-CD3/CD28–Activated T Cells After Transduction with a Retroviral Vector Expressing Herpes Simplex Virus Thymidine Kinase and Truncated Nerve Growth Factor Receptor

“…We sought to test the importance of FBS and human FP in achieving efficient transduction of activated T cells, and documented that FP is a viable alternative to the use of bovine products during the transduction period. It appears that the processing of the plasma as described removes complement or other agents that have been described to interfere retroviral mediated gene transfer (Shimizu et al, 1995). The role of IL-2 in the optimization of the expansion and subsequent function of transduced and selected T cells remains unclear.…”

In situ Perfusion of the Liver Enhances the Efficiency of Retrovirus-Mediated Gene Transfer to Hepatocytes

“…As an alternative to these ex vivo procedures, the systemic or portal injection of the vector was tested in several reports [11]. However, the injected vector solution is known to greatly suffer immediate dilution by the circulating blood and is also eliminated with the Tomori/Shiraishi/Muto circulating complement, thus resulting in poor efficiency of gene transfer [12].…”

“…We have further applied this procedure to the liver in vivo, using both in situ perfusion of the liver and adenoviral vector under cold hepatic ischemia resulting in efficient gene transfer [6,7]. The objective in these ex vivo and in situ models of gene transfer was to enable the liver to be infected with a high titer of viral vector for a long time, without either being diluted by the blood circulation in the target organ [12] or sacrificing the hepatic function [6], or without being attacked by the circulating complement [6]. Based on these facts, we used the in situ perfusion of the liver as a tool for improving the efficiency of traditional retrovirus-mediated gene transfer into the regenerative liver.…”

Stable Gene Expression with VSV-G Pseudotyped-Retrovirus Vector in the Rat Liver

“…This ex vivo procedure was also applicable in a gene transfer targeting the self-liver in vivo, in which the liver was isolated from the systemic circulation under a portsystemic shunt and remained in contact with the virus vector under cold ischemia [4]. Since the systemic injection of the virus vector suffers an extensive dilution resulting in a low efficacy of gene transfer and also suffers elimination by the circulating complement [13], the above in situ procedures have an advantage in achieving an efficient gene transfer. As a result, this in situ procedure effectively enhanced the efficiency of retrovirus-mediated gene transfer to the liver in vivo (manuscript in preparation).…”