Synthesis and biological evaluation of immunoconjugates of adriamycin and a human IgM linked by poly[N5-(2-hydroxyethyl)-l-glutamine

C.J.T. Hoes, M. Ankoné, J. Grootoonk, J. Feijen, E. van der Struik, A. van Doornmalen, D. Pham, A. de Man, A. van Ettekoven, I. Schlachter, P.J. Boon, F. Kaspersen, E.S. Bos

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Abstract

The synthesis and purification of radiolabelled immunoconjugates, composed of a human IgM monoclonal antibody (IgM 16.88) directed against an intracellular tumour-associated antigen, the drug carrier poly[N5-(2-hydroxyethyl)--glutamine] (PHEG) and the cytostatic drug adriamycin (ADR) are described. The immunoconjugates were constructed to allow selective release of ADR in the putatively acidic environment of the tumour through a novel acid-labile maleamic acid linker. The conjugate of PHEG and the acid-labile ADR derivative effectively released ADR in cytotoxic amounts at a pH of 6.0 as judged from incubation in buffer and from inhibition of the growth of HT-29 colon tumour cells in vitro. Immunoconjugates were prepared by coupling of PHEG-ADR having a hydrolytically stable amide bond with 131I-labelled antibody through thioether bond formation involving a single thiol group at the C-terminus of the polymer chain and maleimido groups introduced onto the
Original languageEnglish
Pages (from-to)245-266
Number of pages22
JournalJournal of controlled release
Volume38
Issue number38
DOIs
Publication statusPublished - 1996

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