The University of Southampton
University of Southampton Institutional Repository

Epidermal growth factor receptor and g250: useful target antigens for antibody mediated cellular cytotoxicity against renal cell carcinoma?

Epidermal growth factor receptor and g250: useful target antigens for antibody mediated cellular cytotoxicity against renal cell carcinoma?
Epidermal growth factor receptor and g250: useful target antigens for antibody mediated cellular cytotoxicity against renal cell carcinoma?
Purpose: monoclonal antibodies are a novel treatment option for certain tumor patients. We evaluated the potential of antibody derivatives against epidermal growth factor receptor and G250, which are 2 candidate antigens on renal cell carcinoma, to recruit effector cells for killing renal cell carcinoma.
Material and methods: as a measure of cytotoxicity, 51chromium release assays against renal cell carcinoma lines were performed using unseparated blood or isolated cell populations as the source of effectors. Blood was obtained from healthy donors, or from patients receiving granulocyte-macrophage colony-stimulating factor or granulocyte colony-stimulating factor for enhancing effector cell function. Parental human IgG1 antibodies against epidermal growth factor receptor and G250 were compared with respective chemically linked bispecific antibodies targeting IgA Fc receptor FcalphaRI (CD89), a novel cytotoxic trigger molecule on polymorphonuclear cells and monocytes/macrophages, which were constructed by chemically crosslinking appropriate F(ab') fragments.
Results: renal cell carcinoma lines were highly resistant to complement dependent lysis. With mononuclear effector cells high levels of renal cell carcinoma killing were observed with a humanized epidermal growth factor receptor directed monoclonal antibody, while the same antibody did not recruit granulocytes (polymorphonuclear cells) for antibody dependent cell mediated cytotoxicity. However, polymorphonuclear cells effectively lysed renal cell carcinoma with [FcalphaRI x epidermal growth factor receptor] bispecific antibody. FcalphaRI mediated killing was significantly enhanced when the blood of patients on granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor therapy was analyzed. However, G250 mediated only low levels of killing with mononuclear cell but not with polymorphonuclear effector cells.
Conclusions: targeting epidermal growth factor receptor proved to recruit efficiently mononuclear or polymorphonuclear cell mediated killing mechanisms, while G250 directed antibody constructs were significantly less effective. Particularly effective renal cell carcinoma killing was observed with combined [FcalphaRI x epidermal growth factor receptor] bispecific antibody and granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor.
0022-5347
707-712
Stadick, H.
4b280160-ddfb-493d-81bf-6608789f7451
Stockmeyer, B.
0a5efcc1-7b07-4811-85f8-bf916e3a760c
Kuhn, R.
5389190d-d147-4490-85f8-7ffae8be86b5
Schrott, K.M.
615581f6-f206-4465-bdf8-d274d718077c
Kalden, J.R.
4dcbb2f1-76b3-438d-bbc8-27e5853e2999
Glennie, M.J.
9f6f0eff-4560-48c2-80cd-0ec116110ded
Van de Winkel, J.G.
b13150c7-4db5-4a1e-80d4-926eff539b96
Gramatzki, M.
32e3f79e-e626-4690-9192-ee2cc30132d1
Valerius, T.
39a2d564-ac9e-47b6-9030-e6d74dbcdbf5
Elsasser, D.
a8575ce5-26fd-4edc-9f85-829c500183b6
Stadick, H.
4b280160-ddfb-493d-81bf-6608789f7451
Stockmeyer, B.
0a5efcc1-7b07-4811-85f8-bf916e3a760c
Kuhn, R.
5389190d-d147-4490-85f8-7ffae8be86b5
Schrott, K.M.
615581f6-f206-4465-bdf8-d274d718077c
Kalden, J.R.
4dcbb2f1-76b3-438d-bbc8-27e5853e2999
Glennie, M.J.
9f6f0eff-4560-48c2-80cd-0ec116110ded
Van de Winkel, J.G.
b13150c7-4db5-4a1e-80d4-926eff539b96
Gramatzki, M.
32e3f79e-e626-4690-9192-ee2cc30132d1
Valerius, T.
39a2d564-ac9e-47b6-9030-e6d74dbcdbf5
Elsasser, D.
a8575ce5-26fd-4edc-9f85-829c500183b6

Stadick, H., Stockmeyer, B., Kuhn, R., Schrott, K.M., Kalden, J.R., Glennie, M.J., Van de Winkel, J.G., Gramatzki, M., Valerius, T. and Elsasser, D. (2002) Epidermal growth factor receptor and g250: useful target antigens for antibody mediated cellular cytotoxicity against renal cell carcinoma? The Journal of Urology, 167 (2 Pt 1), 707-712.

Record type: Article

Abstract

Purpose: monoclonal antibodies are a novel treatment option for certain tumor patients. We evaluated the potential of antibody derivatives against epidermal growth factor receptor and G250, which are 2 candidate antigens on renal cell carcinoma, to recruit effector cells for killing renal cell carcinoma.
Material and methods: as a measure of cytotoxicity, 51chromium release assays against renal cell carcinoma lines were performed using unseparated blood or isolated cell populations as the source of effectors. Blood was obtained from healthy donors, or from patients receiving granulocyte-macrophage colony-stimulating factor or granulocyte colony-stimulating factor for enhancing effector cell function. Parental human IgG1 antibodies against epidermal growth factor receptor and G250 were compared with respective chemically linked bispecific antibodies targeting IgA Fc receptor FcalphaRI (CD89), a novel cytotoxic trigger molecule on polymorphonuclear cells and monocytes/macrophages, which were constructed by chemically crosslinking appropriate F(ab') fragments.
Results: renal cell carcinoma lines were highly resistant to complement dependent lysis. With mononuclear effector cells high levels of renal cell carcinoma killing were observed with a humanized epidermal growth factor receptor directed monoclonal antibody, while the same antibody did not recruit granulocytes (polymorphonuclear cells) for antibody dependent cell mediated cytotoxicity. However, polymorphonuclear cells effectively lysed renal cell carcinoma with [FcalphaRI x epidermal growth factor receptor] bispecific antibody. FcalphaRI mediated killing was significantly enhanced when the blood of patients on granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor therapy was analyzed. However, G250 mediated only low levels of killing with mononuclear cell but not with polymorphonuclear effector cells.
Conclusions: targeting epidermal growth factor receptor proved to recruit efficiently mononuclear or polymorphonuclear cell mediated killing mechanisms, while G250 directed antibody constructs were significantly less effective. Particularly effective renal cell carcinoma killing was observed with combined [FcalphaRI x epidermal growth factor receptor] bispecific antibody and granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor.

Full text not available from this repository.

More information

Published date: 2002

Identifiers

Local EPrints ID: 26610
URI: http://eprints.soton.ac.uk/id/eprint/26610
ISSN: 0022-5347
PURE UUID: 0b8f1443-fb1a-4a2d-b0c8-adb737493304

Catalogue record

Date deposited: 21 Apr 2006
Last modified: 15 Jul 2019 19:13

Export record

Contributors

Author: H. Stadick
Author: B. Stockmeyer
Author: R. Kuhn
Author: K.M. Schrott
Author: J.R. Kalden
Author: M.J. Glennie
Author: J.G. Van de Winkel
Author: M. Gramatzki
Author: T. Valerius
Author: D. Elsasser

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×