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
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
September 2008
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), .
(doi:10.1002/eji.200838208).
(PMID:18792403)
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
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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
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Date deposited: 09 Mar 2010
Last modified: 14 Mar 2024 02:48
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Author:
Ruth R. French
Author:
Sonya James
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