Multicolumn infusion of gene therapy cells into human brain tumors: technical report.
OBJECTIVE
Effective gene therapy for brain tumors may require saturation of 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 brain. Major disadvantages of this method include the inaccuracy of hand-guided needle placement and limited control of injection parameters. These factors can result in failure to deliver the viral vectors to specifically targeted sites within the brain, extensive tissue disruption resulting from excessively forceful injection, and reflux of the injectate along the needle tract.


METHODS
We describe a novel stereotactic strategy for saturating tumor volumes with tumoricidal doses of gene therapy vectors and a new, more precise method of infusing VPCs. With our new instrument, the multicolumn stereotactic 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.


CONCLUSIONS
This technique should facilitate saturation of tumors with tumoricidal doses of gene therapy vectors and should improve the results of gene therapy protocols that rely on intraparenchymal injection for delivery.
Qureshi
N H
NH
Department of Neurosurgery, Brain Tumor Center, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
Bankiewicz
K S
KS
Louis
D N
DN
Hochberg
F H
FH
Chiocca
E A
EA
Harsh
G R
GR
D001706:Biopsy / Q000009:adverse effects / Q000379:methods; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000175:diagnosis / Q000628:therapy*; D005240:Feasibility Studies; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D007267:Injections / Q000379:methods*; D008279:Magnetic Resonance Imaging; D013238:Stereotaxic Techniques / Q000295:instrumentation