The University of Southampton
University of Southampton Institutional Repository

Treatment with the anti-CD20 antibody (B1) and irradiation result in synergistic cytotoxicity that is dependent on MAPK activation

Ivanov, Andrei, Cragg, Mark S. and Illidge, Tim M. (2006) Treatment with the anti-CD20 antibody (B1) and irradiation result in synergistic cytotoxicity that is dependent on MAPK activation Blood, 108, (11), p.710A.

Record type: Article

Abstract

Radioimmunotherapy using radiolabeled anti-CD20 antibodies (mAb) is an effective new treatment in non-Hodgkin lymphoma with high response rates. However, the molecular mechanisms behind these impressive clinical responses are poorly understood. To elucidate these mechanisms we studied the signaling events evoked in a panel of lymphoma cell lines following treatment with anti-CD20 mAb alone or in combination with irradiation. In all three lymphoma cell-lines tested a synergistic cytotoxic effect was observed when the anti-CD20 mAb B1 was combined with irradiation. The additive effect seen with B1 mAb and radiation was not observed with Rituximab and could be reversed with MEK inhibitors U0126 and PD98059 as well as siRNA targeting MEK1 or 2. Moreover, addition of U0126 reversed the decrease in clonogenic survival triggered by treatment with B1 and irradiation. To further probe the mechanism of this synergistic cell death we used cell lines over-expressing BCL2 or crmA, to block mitochondrial and death receptor pathways, respectively. Although BCL2 and crmA over-expression mediated protection against radiation alone, it had no impact on the increased cytotoxicity induced by B1+irradiation. Morphological studies revealed gross vacuolization of the cytoplasm, yet relatively well preserved nuclei in cells treated with B1+irradiation. Taken together our data indicate that activation of the MAPK cascade is an important factor that contributes to the synergistic effect of anti-CD20 (B1) antibody and irradiation and provides important new insights into how this treatment may work in the clinic.

Full text not available from this repository.

More information

Published date: 16 November 2006
Additional Information: ASH Annual Meeting Abstracts, Poster Board Session: 686-II. Abstract 2508.

Identifiers

Local EPrints ID: 62796
URI: http://eprints.soton.ac.uk/id/eprint/62796
ISSN: 0006-4971
PURE UUID: 1fd6b82d-b06c-4fbb-a121-20071d7c3918
ORCID for Mark S. Cragg: ORCID iD orcid.org/0000-0003-2077-089X

Catalogue record

Date deposited: 10 Nov 2008
Last modified: 17 Jul 2017 14:19

Export record

Contributors

Author: Andrei Ivanov
Author: Mark S. Cragg ORCID iD
Author: Tim M. Illidge

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.

×