Cancer Research Cancer Research Funding Available  Sign up for Cancer Research eTOC's
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

[Cancer Research 49, 613-617, February 1, 1989]
© 1989 American Association for Cancer Research

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ramakrishnan, S.
Right arrow Articles by Houston, L. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ramakrishnan, S.
Right arrow Articles by Houston, L. L.

Recombinant Ricin A Chain Conjugated to Monoclonal Antibodies: Improved Tumor Cell Inhibition in the Presence of Lysosomotropic Compounds

S. Ramakrishnan1, Michael J. Bjorn2 and L. L. Houston3

Cetus Corporation, Emeryville, California 94608

Recombinant ricin A chain was chemically linked to monoclonal antibodies directed toward human breast cancer cells, a human T-cell differentiation antigen, and mouse transferrin receptor. Three types of immunotoxins were prepared; in two of them the antibody was linked to recombinant ricin A chain by a disulfide bond and in the third, a nonreducible thioether bond was used. Immunotoxins containing a nonreducible linkage may have some advantage over conjugates containing a reducible linkage because of improved stability in vivo. Conjugation of recombinant ricin A chain through either the endogenous thiol group or through a derivatized amino group produced immunotoxins with comparable cytotoxicity. The thioether conjugate was 1000-fold less cytotoxic to target tumor cells than the respective disulfide-linked immunotoxin. However, addition of monensin, a monocarboxylic ionophore, greatly enhanced the cytotoxicity of the thioether-linked immunotoxin. Monensin increased the immunotoxin activity better than other lysosomotropic reagents that were tested. The increase in activity of recombinant ricin A chain-containing immunotoxins mediated by monensin argues against a role for contaminating ricin B chain in potentiation.

1 Present address: Department of Medicine, Division of Hematology/Oncology, Duke University Medical Center, Durham, NC 27710.

2 Present address: NeoRx Corporation, 410 Harrison St., Seattle, WA 98119.

3 To whom correspondence should be addressed at Cetus Corporation, 1400 Fifty-third Street, Emeryville, CA 94608.

Received 8/16/88. Revised 10/17/88. Accepted 10/21/88.




This article has been cited by other articles:


Home page
International Journal of ToxicologyHome page
S. Bharadwaj, S. S. Rathore, and P. C. Ghosh
Enhancement of the Cytotoxicity of Liposomal Ricin by the Carboxylic Ionophore Monensin and the Lysosomotropic Amine NH4Cl in Chinese Hamster Ovary Cells
International Journal of Toxicology, September 1, 2006; 25(5): 349 - 359.
[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
Copyright © 1989 by the American Association for Cancer Research.