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T cell immunity to lymphoma following treatment with anti-CD40 monoclonal antibody

T cell immunity to lymphoma following treatment with anti-CD40 monoclonal antibody
T cell immunity to lymphoma following treatment with anti-CD40 monoclonal antibody
In this study we demonstrate that treatment with anti-CD40 mAb eradicates a range of mouse lymphomas (BCL1, A31, A20, and EL4), but only when used against i.v. tumor doses in excess of 107 cells. Only partial protection was seen against smaller tumor loads. We saw no evidence that anti-CD40 mAb changed the phenotype of the lymphomas or inhibited their growth in the initial period following treatment, but it did result in a rapid expansion of cytotoxic CD8+ cells that was able to clear the neoplastic disease and provide long-term protection against tumor rechallenge. The CTL responses were blocked by mAb against a range of coreceptors and cytokines, including CD8, B7-1, B7-2, LFA-1, and IFN-{gamma}, but not CD4 or CTLA-4, indicating the presence of a conventional cellular Th1 response. Furthermore, we found evidence of cross-recognition between lymphomas (BCL1 and A20) as measured by cytotoxicity and IFN-{gamma} responses in vitro and using tumor rechallenge experiments, suggesting common target Ags. Finally, although anti-CD40 was shown to stimulate NK cell killing, we could find no role for these cells in controlling tumor growth. These data underline the ability of anti-CD40 mAb to potentiate CTL responses and the potency of cellular immunity in eradicating large quantities of syngeneic tumor.
0022-1767
2720-2728
Tutt, Alison L.
46ce577b-aea1-412d-84ea-fc4dab794469
O'Brien, Lyn
0dea42f9-e160-4929-80db-35001165c280
Hussain, Akmal
990fe7ed-e70b-43b6-b230-a9bb660a1224
Crowther, Graham R.
0ef62e5c-2b5d-4c31-a3a5-8e74c23e024b
French, Ruth R.
a95ea7a1-7aeb-4c20-998e-fde663613fd1
Glennie, Martin J.
9f6f0eff-4560-48c2-80cd-0ec116110ded
Tutt, Alison L.
46ce577b-aea1-412d-84ea-fc4dab794469
O'Brien, Lyn
0dea42f9-e160-4929-80db-35001165c280
Hussain, Akmal
990fe7ed-e70b-43b6-b230-a9bb660a1224
Crowther, Graham R.
0ef62e5c-2b5d-4c31-a3a5-8e74c23e024b
French, Ruth R.
a95ea7a1-7aeb-4c20-998e-fde663613fd1
Glennie, Martin J.
9f6f0eff-4560-48c2-80cd-0ec116110ded

Tutt, Alison L., O'Brien, Lyn, Hussain, Akmal, Crowther, Graham R., French, Ruth R. and Glennie, Martin J. (2002) T cell immunity to lymphoma following treatment with anti-CD40 monoclonal antibody. The Journal of Immunology, 168 (6), 2720-2728.

Record type: Article

Abstract

In this study we demonstrate that treatment with anti-CD40 mAb eradicates a range of mouse lymphomas (BCL1, A31, A20, and EL4), but only when used against i.v. tumor doses in excess of 107 cells. Only partial protection was seen against smaller tumor loads. We saw no evidence that anti-CD40 mAb changed the phenotype of the lymphomas or inhibited their growth in the initial period following treatment, but it did result in a rapid expansion of cytotoxic CD8+ cells that was able to clear the neoplastic disease and provide long-term protection against tumor rechallenge. The CTL responses were blocked by mAb against a range of coreceptors and cytokines, including CD8, B7-1, B7-2, LFA-1, and IFN-{gamma}, but not CD4 or CTLA-4, indicating the presence of a conventional cellular Th1 response. Furthermore, we found evidence of cross-recognition between lymphomas (BCL1 and A20) as measured by cytotoxicity and IFN-{gamma} responses in vitro and using tumor rechallenge experiments, suggesting common target Ags. Finally, although anti-CD40 was shown to stimulate NK cell killing, we could find no role for these cells in controlling tumor growth. These data underline the ability of anti-CD40 mAb to potentiate CTL responses and the potency of cellular immunity in eradicating large quantities of syngeneic tumor.

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Published date: March 2002

Identifiers

Local EPrints ID: 26648
URI: http://eprints.soton.ac.uk/id/eprint/26648
ISSN: 0022-1767
PURE UUID: ded0a4f0-b4a5-4514-a73b-e512a46ee3d6

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Date deposited: 21 Apr 2006
Last modified: 16 Dec 2019 19:22

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