Direct stereotactic intracerebral injection of monoclonal antibodies and their fragments: a potential approach to brain tumor immunotherapy.
Delivery of monoclonal antibodies (Mab) to brain tumors is restricted by the blood:brain barrier. To circumvent this problem, we studied direct stereotactic injection of the Mab into the brain. An anti-melanoma intact Mab and its Fab fragments, which do not react with normal rat brain, were radioiodinated and injected either intracerebrally (IC) or intravenously (IV) into rats. At 5 days after injection, IC delivery of intact antibody was 101 times higher than IV delivery. The ratio of radioantibody in injected cerebrum:blood was 14:1. With IC delivered Fab fragments, the radioantibody ratio in injected cerebrum:blood was 242:1 at 5 days after IC injection, with a 680-fold delivery advantage over IV injection. These data demonstrate a dramatic regional delivery advantage for intact Mab and especially for Fab fragments injected directly into the brain. This route of Mab delivery may have therapeutic potential for brain tumors.
Liebert
M
M
Department of Surgery, University of Michigan, Ann Arbor 48109.
Wahl
R L
RL
Lawless
G
G
McKeever
P E
PE
Taren
J A
JA
Beierwaltes
W H
WH
Brasswell
R
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000628:therapy*; D005260:Female; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D007457:Iodine Radioisotopes; D008546:Melanoma, Experimental / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D013238:Stereotaxic Techniques; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes