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

doi: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

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 language	English
Pages (from-to)	245-266
Number of pages	22
Journal	Journal of controlled release
Volume	38
Issue number	38
DOIs	https://doi.org/10.1016/0168-3659(95)00126-3
Publication status	Published - 1996

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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. (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, 38(38), 245-266. https://doi.org/10.1016/0168-3659(95)00126-3

@article{8bf546e37e724496b27ccf92c9a42ba3,

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

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",

language = "English",

volume = "38",

pages = "245--266",

journal = "Journal of controlled release",

issn = "0168-3659",

publisher = "Elsevier",

number = "38",

}

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

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

SN - 0168-3659

VL - 38

SP - 245

EP - 266

JO - Journal of controlled release

JF - Journal of controlled release

IS - 38

ER -