Multicolumn infusion of gene therapy cells into human brain tumors: Technical report

OBJECTIVE: Effective gene therapy for brain tumors may require saturation o f the tumors with tumoricidal doses of the therapeutic gene. Safe, precise, and efficient delivery of gene therapy vectors is required. Most reported cases of and published protocols for gene therapy for brain tumors involve freehand injection of retroviral vector-producing cells (VPCs) into the bra in. Major disadvantages of this method include the inaccuracy of hand-guide d needle placement and limited control of injection parameters. These facto rs can result in failure to deliver the viral vectors to specifically targe ted sites within the brain, extensive tissue disruption resulting from exce ssively forceful injection, and reflux of the injectate along the needle tr act. METHODS: We describe a novel stereotactic strategy for saturating tumor vol umes with tumoricidal doses of gene therapy vectors and a new, more precise method of infusing VPCs. With our new instrument, the multicolumn stereota ctic infusion system, needle placement is stereotactically guided and both VPC infusion and needle withdrawal are mechanically controlled. RESULTS: This technique, which has been used effectively for six patients, permits precise deposition of columns of VPCs throughout the targeted tumor volume. CONCLUSION: This technique should facilitate saturation of tumors with tumo ricidal doses of gene therapy vectors and should improve the results of gen e therapy protocols that rely on intraparenchymal injection for delivery.