Skip to main content
Journal cover image

Improved antitumor activity of a recombinant anti-Lewis(y) immunotoxin not requiring proteolytic activation.

Publication ,  Journal Article
Kuan, CT; Pastan, I
Published in: Proc Natl Acad Sci U S A
February 6, 1996

B1(dsFv)-PE33 is a recombinant immunotoxin composed of a mutant form of Pseudomonas exotoxin (PE) that does not need proteolytic activation and a disulfide-stabilized Fv fragment of the anti-Lewis(y) monoclonal antibody B1, which recognizes a carbohydrate epitope on human carcinoma cells. In this molecule, amino acids 1-279 of PE are deleted and domain Ib (amino acids 365-394) is replaced by the heavy chain variable region (VH) domain of monoclonal antibody B1. The light chain (VL) domain is connected to the VH domain by a disulfide bond. This recombinant toxin, termed B1(dsFv)-PE33, does not require proteolytic activation and it is smaller than other immunotoxins directed at Lewis(y), all of which require proteolytic activation. Furthermore, it is more cytotoxic to antigen-positive cell lines. B1(dsFv)-PE38 has the highest antitumor activity of anti-Lewis(y) immunotoxins previously constructed. B1(dsFv)-PE33 caused complete regression of tumors when given at 12 micrograms/kg (200 pmol/kg) every other day for three doses, whereas B1(dsFv)-PE38 did not cause regressions at 13 micrograms/kg (200 pmol/kg). By bypassing the need for proteolytic activation and decreasing molecular size we have enlarged the therapeutic window for the treatment of human cancers growing in mice, so that complete remissions are observed at 2.5% of the LD50.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

February 6, 1996

Volume

93

Issue

3

Start / End Page

974 / 978

Location

United States

Related Subject Headings

  • Virulence Factors
  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Stomach Neoplasms
  • Recombinant Proteins
  • Pseudomonas aeruginosa Exotoxin A
  • Pseudomonas aeruginosa
  • Prostatic Neoplasms
  • Polymerase Chain Reaction
  • Mutagenesis, Site-Directed
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kuan, C. T., & Pastan, I. (1996). Improved antitumor activity of a recombinant anti-Lewis(y) immunotoxin not requiring proteolytic activation. Proc Natl Acad Sci U S A, 93(3), 974–978. https://doi.org/10.1073/pnas.93.3.974
Kuan, C. T., and I. Pastan. “Improved antitumor activity of a recombinant anti-Lewis(y) immunotoxin not requiring proteolytic activation.Proc Natl Acad Sci U S A 93, no. 3 (February 6, 1996): 974–78. https://doi.org/10.1073/pnas.93.3.974.
Kuan, C. T., and I. Pastan. “Improved antitumor activity of a recombinant anti-Lewis(y) immunotoxin not requiring proteolytic activation.Proc Natl Acad Sci U S A, vol. 93, no. 3, Feb. 1996, pp. 974–78. Pubmed, doi:10.1073/pnas.93.3.974.
Kuan CT, Pastan I. Improved antitumor activity of a recombinant anti-Lewis(y) immunotoxin not requiring proteolytic activation. Proc Natl Acad Sci U S A. 1996 Feb 6;93(3):974–978.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

February 6, 1996

Volume

93

Issue

3

Start / End Page

974 / 978

Location

United States

Related Subject Headings

  • Virulence Factors
  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Stomach Neoplasms
  • Recombinant Proteins
  • Pseudomonas aeruginosa Exotoxin A
  • Pseudomonas aeruginosa
  • Prostatic Neoplasms
  • Polymerase Chain Reaction
  • Mutagenesis, Site-Directed