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

Publication ,  Journal Article
Pastan, IH; Archer, GE; McLendon, RE; Friedman, HS; Fuchs, HE; Wang, QC; Pai, LH; Herndon, J; Bigner, DD
Published in: Proc Natl Acad Sci U S A
March 28, 1995

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.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

March 28, 1995

Volume

92

Issue

7

Start / End Page

2765 / 2769

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Time Factors
  • Rats, Nude
  • Rats
  • Mice
  • Meningitis
  • Injections, Spinal
  • Immunotoxins
  • Humans
 

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Pastan, I. H., Archer, G. E., McLendon, R. E., Friedman, H. S., Fuchs, H. E., Wang, Q. C., … Bigner, D. D. (1995). Intrathecal administration of single-chain immunotoxin, LMB-7 [B3(Fv)-PE38], produces cures of carcinomatous meningitis in a rat model. Proc Natl Acad Sci U S A, 92(7), 2765–2769. https://doi.org/10.1073/pnas.92.7.2765
Pastan, I. H., G. E. Archer, R. E. McLendon, H. S. Friedman, H. E. Fuchs, Q. C. Wang, L. H. Pai, J. Herndon, and D. D. Bigner. “Intrathecal administration of single-chain immunotoxin, LMB-7 [B3(Fv)-PE38], produces cures of carcinomatous meningitis in a rat model.Proc Natl Acad Sci U S A 92, no. 7 (March 28, 1995): 2765–69. https://doi.org/10.1073/pnas.92.7.2765.
Pastan IH, Archer GE, McLendon RE, Friedman HS, Fuchs HE, Wang QC, et al. Intrathecal administration of single-chain immunotoxin, LMB-7 [B3(Fv)-PE38], produces cures of carcinomatous meningitis in a rat model. Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2765–9.
Pastan, I. H., et al. “Intrathecal administration of single-chain immunotoxin, LMB-7 [B3(Fv)-PE38], produces cures of carcinomatous meningitis in a rat model.Proc Natl Acad Sci U S A, vol. 92, no. 7, Mar. 1995, pp. 2765–69. Pubmed, doi:10.1073/pnas.92.7.2765.
Pastan IH, Archer GE, McLendon RE, Friedman HS, Fuchs HE, Wang QC, Pai LH, Herndon J, Bigner DD. Intrathecal administration of single-chain immunotoxin, LMB-7 [B3(Fv)-PE38], produces cures of carcinomatous meningitis in a rat model. Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2765–2769.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

March 28, 1995

Volume

92

Issue

7

Start / End Page

2765 / 2769

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Time Factors
  • Rats, Nude
  • Rats
  • Mice
  • Meningitis
  • Injections, Spinal
  • Immunotoxins
  • Humans