title: Intrathecal administration of single-chain immunotoxin, LMB-7 [B3(Fv)-PE38], produces cures of carcinomatous meningitis in a rat model.
abstract: LMB-7 [B3(Fv)-PE38] is a single-chain immunotoxin constructed from the murine monoclonal antibody B3 and a truncated from of Pseudomonas exotoxin PE38. Antibody B3 recognizes a carbohydrate epitope found on solid tumors that frequently invade the intrathecal space and cause neoplastic meningitis. We tested the therapeutic value of intrathecally administered LMB-7 by using a model of human neoplastic meningitis in athymic rats. This model is representative of a clinical situation in that antibody B3 cross-reacts with a number of normal tissues that can be used to monitor potential systemic toxicity. Treatment was begun 3 days after A431 tumor implantation. Without treatment, the animals median survival was 10 days. Intrathecal administration of 10 micrograms of LMB-7 in 40 microliters on days 3, 5, and 7 produced 4 of 10 and 8 of 10 long-term survivors (> 170 days) in two experiments. Of the long-term survivors, 2 of 4 and 7 of 8 survivors had no microscopic evidence of tumor and were considered histologic cures. Lack of significant toxicity in the effective dose range and specificity make LMB-7 an excellent candidate for intrathecal treatment of neoplastic meningitis in humans.
authors.affiliation: Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA.
authors.forename: I H
authors.initials: IH
authors.lastname: Pastan
authors.forename: G E
authors.initials: GE
authors.lastname: Archer
authors.forename: R E
authors.initials: RE
authors.lastname: McLendon
authors.forename: H S
authors.initials: HS
authors.lastname: Friedman
authors.forename: H E
authors.initials: HE
authors.lastname: Fuchs
authors.forename: Q C
authors.initials: QC
authors.lastname: Wang
authors.forename: L H
authors.initials: LH
authors.lastname: Pai
authors.forename: J
authors.initials: J
authors.lastname: Herndon
authors.forename: D D
authors.initials: DD
authors.lastname: Bigner
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D002294:Carcinoma, Squamous Cell / Q000503:physiopathology*; D005098:Exotoxins; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D007278:Injections, Spinal; D008581:Meningitis / Q000188:drug therapy* / Q000209:etiology; D051379:Mice; D051381:Rats; D011923:Rats, Nude; D013997:Time Factors; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D005098:Exotoxins; D000922:Immunotoxins; C092978:immunotoxin LMB-7