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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Immunoconjugates
Glutamine
Doxorubicin
Immunoglobulin M
Drug Carriers
Acids
Cytostatic Agents
Neoplasm Antigens
Sulfides
Sulfhydryl Compounds
Amides
Neoplasms
Buffers
Polymers
Colon
Monoclonal Antibodies
Antibodies
Growth
poly-N(5)-(2-hydroxyethyl)glutamine

Cite this

Hoes, C.J.T. ; Ankoné, M. ; Grootoonk, J. ; Feijen, J. ; van der Struik, E. ; van Doornmalen, A. ; Pham, D. ; de Man, A. ; van Ettekoven, A. ; Schlachter, I. ; Boon, P.J. ; Kaspersen, F. ; Bos, E.S. / Synthesis and biological evaluation of immunoconjugates of adriamycin and a human IgM linked by poly[N5-(2-hydroxyethyl)-l-glutamine. In: Journal of controlled release. 1996 ; Vol. 38, No. 38. pp. 245-266.
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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",
author = "C.J.T. Hoes and M. Ankon{\'e} and J. Grootoonk and J. Feijen and {van der Struik}, E. and {van Doornmalen}, A. and D. Pham and {de Man}, A. and {van Ettekoven}, A. and I. Schlachter and P.J. Boon and F. Kaspersen and E.S. Bos",
year = "1996",
doi = "10.1016/0168-3659(95)00126-3",
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Hoes, CJT, Ankoné, M, Grootoonk, J, Feijen, J, van der Struik, E, van Doornmalen, A, Pham, D, de Man, A, van Ettekoven, A, Schlachter, I, Boon, PJ, Kaspersen, F & Bos, ES 1996, 'Synthesis and biological evaluation of immunoconjugates of adriamycin and a human IgM linked by poly[N5-(2-hydroxyethyl)-l-glutamine' Journal of controlled release, vol. 38, no. 38, pp. 245-266. https://doi.org/10.1016/0168-3659(95)00126-3

Synthesis and biological evaluation of immunoconjugates of adriamycin and a human IgM linked by poly[N5-(2-hydroxyethyl)-l-glutamine. / Hoes, C.J.T.; Ankoné, M.; Grootoonk, J.; Feijen, J.; van der Struik, E.; van Doornmalen, A.; Pham, D.; de Man, A.; van Ettekoven, A.; Schlachter, I.; Boon, P.J.; Kaspersen, F.; Bos, E.S.

In: Journal of controlled release, Vol. 38, No. 38, 1996, p. 245-266.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Synthesis and biological evaluation of immunoconjugates of adriamycin and a human IgM linked by poly[N5-(2-hydroxyethyl)-l-glutamine

AU - Hoes, C.J.T.

AU - Ankoné, M.

AU - Grootoonk, J.

AU - Feijen, J.

AU - van der Struik, E.

AU - van Doornmalen, A.

AU - Pham, D.

AU - de Man, A.

AU - van Ettekoven, A.

AU - Schlachter, I.

AU - Boon, P.J.

AU - Kaspersen, F.

AU - Bos, E.S.

PY - 1996

Y1 - 1996

N2 - 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

AB - 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

U2 - 10.1016/0168-3659(95)00126-3

DO - 10.1016/0168-3659(95)00126-3

M3 - Article

VL - 38

SP - 245

EP - 266

JO - Journal of controlled release

JF - Journal of controlled release

SN - 0168-3659

IS - 38

ER -