Intrathecal administration of single-chain immunotoxin, LMB-7 [B3(Fv)-PE38], produces cures of carcinomatous meningitis in a rat model.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Pastan, IH; Archer, GE; McLendon, RE; Friedman, HS; Fuchs, HE; Wang, QC; Pai, LH; Herndon, J; Bigner, DD

Published Date

  • March 28, 1995

Published In

Volume / Issue

  • 92 / 7

Start / End Page

  • 2765 - 2769

PubMed ID

  • 7708720

International Standard Serial Number (ISSN)

  • 0027-8424

Language

  • eng

Conference Location

  • United States