This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Garnett, M. C. Articles by Baldwin, R. W. Search for Related Content PubMed PubMed Citation Articles by Garnett, M. C. Articles by Baldwin, R. W.

An Improved Synthesis of a Methotrexate-Albumin-791T/36 Monoclonal Antibody Conjugate Cytotoxic to Human Osteogenic Sarcoma Cell Lines¹

Cancer Research Campaign Laboratories, University of Nottingham, University Park, Nottingham, NG7 2RD, United Kingdom

Improvements have been made in the synthesis of a drug-carrier-antibody conjugate using methotrexate as the drug, human serum albumin as the carrier, and a monoclonal antibody against a human osteogenic sarcoma cell line (791T/36). The improvements have resulted in a higher and more reproducible substitution of serum albumin by methotrexate, and improvements in the coupling of methotrexate covalently linked to human serum albumin to antibody resulting in a greater ease and efficiency of conjugation. The improvements have led to a conjugate of increased cytotoxicity while retaining the previously reported specificity. A conjugate is reported which shows cytotoxicity of 1.1 ng/ml (2.4 nM) with respect to methotrexate and 6 x 10^-11 M with respect to antibody in a clonogenic assay on 791T cells. This cytotoxicity is greater than that obtained using free methotrexate (2.8 ng/ml; 6.1 nM) and implies that drug cytotoxicity can be considered as the sum of drug uptake and the number of drug molecules required to kill a cell. This further suggests that antibodies could provide a potent delivery system for drugs which are poorly taken up by cells.

¹ This work was supported by a grant from the Cancer Research Campaign, United Kingdom.

² To whom requests for reprints should be addressed.

Received 4/ 8/85. Revised 10/21/85. Accepted 11/ 6/85.

This article has been cited by other articles:

				N. Umemoto, Y. Kato, and T. Hara Review : Molecular Design of Methotrexate-Antibody Conjugates for Targeted Cancer Treatment Journal of Bioactive and Compatible Polymers, January 1, 1992; 7(2): 191 - 219. [PDF]

				R. O. Dillman Monoclonal Antibodies for Treating Cancer Ann Intern Med, October 1, 1989; 111(7): 592 - 603. [Abstract] [PDF]