Abstract
Patients with recurrent malignant brain cancer, who were receiving gene therapy by intracerebral injection of murine retroviral vector producer cells (VPCs), were monitored for the presence of replication-competent retrovirus (RCR). RCR sequences were not detected by polymerase chain reaction (PCR) in any of the 608 peripheral blood leukocyte (PBL) samples analyzed. Vector DNA sequences were detected transiently in PBL samples from a subset of 34 patients. Humoral immune responses to a retroviral core protein p30 and murine VPC were detected in some patients, most frequently in patients receiving repeated administrations of VPC. RCR was not detected in biological assays of PBLs from 41 patients who had either anti-retroviral antibodies in sera and/or vector DNA in PBLs. Our data suggest that in situ generation of RCR was not detected following intracerebral inoculation of VPCs in any of the 128 patients evaluated.
Overview summary
Much discussion has taken place on the relative safety of retroviral vectors, which are used in approximately 70% of human studies conducted to date. Most regulatory recommendations on patient safety monitoring are based on the findings of lymphomas that occurred in monkeys following administrations of large doses of RCR (Donahue et al., 1992). The present study involved the intracerebral inoculation of 109 murine retroviral producer cells in patients with brain tumors. Our data indicate that no RCR was detected in more than 1200 blood and serum specimens analyzed. These results are particularly encouraging because patients receiving vector producer cells may have a greater potential exposure to RCR generation in situ than patients receiving retroviral vectors alone.
Get full access to this article
View all access options for this article.