| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Drug Targeting Laboratory, Imperial Cancer Research Fund, Lincoln's Inn Fields, Holborn, WC2A 3PX, London, England
The carbohydrate present on ricin A chain causes ricin A chain immunotoxins to be cleared rapidly in animals by the reticuloendothelial system. In an effort to overcome this problem we destroyed the carbohydrate on ricin A chain by treating it with a mixture of sodium metaperiodate and sodium cyanoborohydride and then linked the "deglycosylated" A chain to monoclonal anti-Thy 1.1 antibody. The deglycosylation procedure did not affect the ability of the A chain component of the immunotoxin to inhibit protein synthesis in a cell-free system or the capacity of the immunotoxin to inhibit protein synthesis in Thy-1.1 positive lymphoma cells in vitro.
Immunotoxins prepared with deglycosylated A chain were cleared from the bloodstream of mice more slowly than native ricin A chain immunotoxins. The difference in the blood clearance rates of the two immunotoxins could be accounted for by a decreased entrapment of the deglycosylated ricin A chain immunotoxin by the liver. Both immunotoxins broke down in vivo with the appearance of free antibody in the bloodstream. The site of cleavage of the immunotoxin was possibly the liver because immunotoxins taken up by it rapidly became unreactive with antiricin but retained reactivity with anti-mouse immunoglobulin G suggesting that dissociation of the A chain from the antibody had occurred. The immunotoxins taken up by the liver were metabolized further and the acid insoluble radioactive metabolites gradually accumulated in the stomach, thyroid, and salivary gland.
The deglycosylated ricin A chain immunotoxin should be a more effective antitumor agent in vivo because it is cleared from the blood more slowly and so has greater opportunity to localize within the tumor target.
1 To whom requests for reprints should be addressed.
Received 7/ 3/86. Revised 10/15/86. Accepted 10/23/86.
This article has been cited by other articles:
|
|
 |
|
  J. Schindler, E. Sausville, R. Messmann, J. W. Uhr, and E. S. Vitetta The Toxicity of Deglycosylated Ricin A Chain-containing Immunotoxins in Patients with Non-Hodgkin's Lymphoma Is Exacerbated by Prior Radiotherapy: A Retrospective Analysis of Patients in Five Clinical Trials Clin. Cancer Res., February 1, 2001; 7(2): 255 - 258. [Abstract] [Full Text]
|
|
|
|
 |
|
 D. Maciejewski-Lenoir, S. C. Heinrichs, X.-J. Liu, N. Ling, A. Tucker, Q. Xie, D. A. Lappi, and D. E. Grigoriadis Selective Impairment of Corticotropin-Releasing Factor1 (CRF1) Receptor-Mediated Function Using CRF Coupled to Saporin Endocrinology, February 1, 2000; 141(2): 498 - 504. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G. Rosenblum, L. K. Shawver, J. W. Marks, J. Brink, L. Cheung, and B. Langton-Webster Recombinant Immunotoxins Directed against the c-erb-2/HER2/neu Oncogene Product: In Vitro Cytotoxicity, Pharmacokinetics, and in Vivo Efficacy Studies in Xenograft Models Clin. Cancer Res., April 1, 1999; 5(4): 865 - 874. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Vitetta, R. Fulton, R. May, M Till, and J. Uhr Redesigning nature's poisons to create anti-tumor reagents Science, November 20, 1987; 238(4830): 1098 - 1104. [Abstract] [PDF]
|
|
|
|
 |
|
 S. F. Atkinson, T. Bettinger, L. W. Seymour, J.-P. Behr, and C. M. Ward Conjugation of Folate via Gelonin Carbohydrate Residues Retains Ribosomal-inactivating Properties of the Toxin and Permits Targeting to Folate Receptor Positive Cells J. Biol. Chem., July 20, 2001; 276(30): 27930 - 27935. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
