The University of Southampton
University of Southampton Institutional Repository

Optimising anti-tumour CD8 T-cell responses using combinations of immunomodulatory antibodies

Optimising anti-tumour CD8 T-cell responses using combinations of immunomodulatory antibodies
Optimising anti-tumour CD8 T-cell responses using combinations of immunomodulatory antibodies
Immunostimulatory mAb as vaccine adjuvants for the treatment of cancer hold considerable potential for boosting weak responses when used against immunogenic tumours, or in combination with various other vaccines. We now show that when administered with OVA, the combination of anti-4-1BB mAb with anti-CD40, anti-OX40 or anti-CD25 resulted in a fourfold enhancement in the antigen-specific T-cell response compared with anti-4-1BB mAb alone, with a similar enhancement in memory responses following rechallenge with OVA. Although the number of antigen-specific T-cells generated after treatment with each of the combinations was similar, marked functional differences were detected. In particular, anti-4-1BB/anti-CD25 resulted in excellent expansion of specific CD8+ T cells but produced fewer IFN-gamma-secreting effector cells than the other combinations. Anti-4-1BB/anti-OX40 proved to be the most potent, inducing the most effective T-cell responses in the RIPmOVA diabetes model with adoptively transferred OVA-specific T cells, and, when given with a peptide vaccine, protecting mice against the poorly immunogenic B16-F10 tumour. Overall the results suggest that although these combinations of mAb look promising in terms of their therapeutic potential, further functional assays are needed to compare their effects
4-1BB, CD40, immunostimulatory mAb, OX40, tumour immunotherapy
0014-2980
2499-2511
Gray, Juliet C.
12d5e17c-97bb-4d6d-8fc4-3914b730ed42
French, Ruth R.
a95ea7a1-7aeb-4c20-998e-fde663613fd1
James, Sonya
764c80e3-5bea-4b34-a871-b43f87ef97b0
Al-Shamkhani, Aymen
0a40b3ce-9d71-4d41-9369-7212f0a84504
Johnson, Peter W.
3f6068ce-171e-4c2c-aca9-dc9b6a37413f
Glennie, Martin J.
9f6f0eff-4560-48c2-80cd-0ec116110ded
Gray, Juliet C.
12d5e17c-97bb-4d6d-8fc4-3914b730ed42
French, Ruth R.
a95ea7a1-7aeb-4c20-998e-fde663613fd1
James, Sonya
764c80e3-5bea-4b34-a871-b43f87ef97b0
Al-Shamkhani, Aymen
0a40b3ce-9d71-4d41-9369-7212f0a84504
Johnson, Peter W.
3f6068ce-171e-4c2c-aca9-dc9b6a37413f
Glennie, Martin J.
9f6f0eff-4560-48c2-80cd-0ec116110ded

Gray, Juliet C., French, Ruth R., James, Sonya, Al-Shamkhani, Aymen, Johnson, Peter W. and Glennie, Martin J. (2008) Optimising anti-tumour CD8 T-cell responses using combinations of immunomodulatory antibodies. European Journal of Immunology, 38 (9), 2499-2511. (doi:10.1002/eji.200838208). (PMID:18792403)

Record type: Article

Abstract

Immunostimulatory mAb as vaccine adjuvants for the treatment of cancer hold considerable potential for boosting weak responses when used against immunogenic tumours, or in combination with various other vaccines. We now show that when administered with OVA, the combination of anti-4-1BB mAb with anti-CD40, anti-OX40 or anti-CD25 resulted in a fourfold enhancement in the antigen-specific T-cell response compared with anti-4-1BB mAb alone, with a similar enhancement in memory responses following rechallenge with OVA. Although the number of antigen-specific T-cells generated after treatment with each of the combinations was similar, marked functional differences were detected. In particular, anti-4-1BB/anti-CD25 resulted in excellent expansion of specific CD8+ T cells but produced fewer IFN-gamma-secreting effector cells than the other combinations. Anti-4-1BB/anti-OX40 proved to be the most potent, inducing the most effective T-cell responses in the RIPmOVA diabetes model with adoptively transferred OVA-specific T cells, and, when given with a peptide vaccine, protecting mice against the poorly immunogenic B16-F10 tumour. Overall the results suggest that although these combinations of mAb look promising in terms of their therapeutic potential, further functional assays are needed to compare their effects

This record has no associated files available for download.

More information

Published date: September 2008
Keywords: 4-1BB, CD40, immunostimulatory mAb, OX40, tumour immunotherapy
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 73438
URI: http://eprints.soton.ac.uk/id/eprint/73438
ISSN: 0014-2980
PURE UUID: 9a37f602-405c-45f6-8f5a-790f3d950f72
ORCID for Juliet C. Gray: ORCID iD orcid.org/0000-0002-5652-4722
ORCID for Aymen Al-Shamkhani: ORCID iD orcid.org/0000-0003-0727-4189
ORCID for Peter W. Johnson: ORCID iD orcid.org/0000-0003-2306-4974

Catalogue record

Date deposited: 09 Mar 2010
Last modified: 14 Mar 2024 02:48

Export record

Altmetrics

Contributors

Author: Juliet C. Gray ORCID iD
Author: Ruth R. French
Author: Sonya James

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.

×