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Anti-tumour immunity in a model of acute myeloid leukaemia

Anti-tumour immunity in a model of acute myeloid leukaemia
Anti-tumour immunity in a model of acute myeloid leukaemia
Whole-cell vaccines allow the induction of anti-tumor immune responses without the need to define tumor antigens. We wished to directly compare, for the first time, the capacity of B7-1, B7-2 and 4-1BB ligand (4-1BBL) costimulatory molecules to convert murine and human acute myeloid leukemia (AML) cells into whole vaccines. 32Dc-kit is a murine myeloid cell line, which develops an AML-like disease over a protracted period, emulating human AML disease development. 32Dc-kit cells were modified to express elevated levels of B7-1, B7-2 or 4-1BBL, and each led to tumor rejection, although only mice injected with 32Dc-kit/B7-2 cells were able to reject subsequent parental tumor cell challenge. T-cell deficient nude mice were able to reject the 32Dc-kit variants, but they could not reject parental cell challenge; however, we found no evidence of cytotoxic T lymphocyte or natural killer (NK) activity ex vivo suggesting that tumor cell killing was mediated by an immune response that could not be recapitulated using purified NK or T cells as lone effectors. In human allogeneic mixed lymphocyte reactions (MLRs), we found no single costimulatory molecule was more effective, suggesting that the induction of a universal anti-tumor response will require a combination of ostimulatory molecules
costimulation, acute myeloid leukaemia, B7-1/CD80, B7-2/CD86, 4-1BB/CD137, immune gene therapy, whole cell vaccine, mouse, human, NK cells
1042-8194
447-454
Cheuk, Adam T.C.
fd9f3583-c275-435d-9878-ebc58eaa1d97
Wells, James W.
97a0a070-701b-46b0-81ba-9725595eb4e8
Chan, Lucas
c134b358-dbcb-4f96-95fd-c7c2d43a9ee9
Westwood, Nigel B.
cbe7bf7f-6ac4-4422-88a3-8c28b65f517c
Berger, Stuart A.
a2c10a23-73a1-47bd-bc7a-ff83aca6bf25
Yagita, Hideo
00a66ce4-d0bf-464f-a28c-20dd2fd652ec
Okumura, Ko
3f6ccb82-6b44-4d6e-961a-ecbc5737296e
Farzin, Farzin
3dd631c7-1b0b-4208-9412-86c9122a541a
Mufti, Ghulam J.
940de420-bc41-4006-8517-f2c926ba70aa
Guinn, Barbara-Anne
30699e61-6fbf-42bf-a594-01fe20d9cb0c
Cheuk, Adam T.C.
fd9f3583-c275-435d-9878-ebc58eaa1d97
Wells, James W.
97a0a070-701b-46b0-81ba-9725595eb4e8
Chan, Lucas
c134b358-dbcb-4f96-95fd-c7c2d43a9ee9
Westwood, Nigel B.
cbe7bf7f-6ac4-4422-88a3-8c28b65f517c
Berger, Stuart A.
a2c10a23-73a1-47bd-bc7a-ff83aca6bf25
Yagita, Hideo
00a66ce4-d0bf-464f-a28c-20dd2fd652ec
Okumura, Ko
3f6ccb82-6b44-4d6e-961a-ecbc5737296e
Farzin, Farzin
3dd631c7-1b0b-4208-9412-86c9122a541a
Mufti, Ghulam J.
940de420-bc41-4006-8517-f2c926ba70aa
Guinn, Barbara-Anne
30699e61-6fbf-42bf-a594-01fe20d9cb0c

Cheuk, Adam T.C., Wells, James W., Chan, Lucas, Westwood, Nigel B., Berger, Stuart A., Yagita, Hideo, Okumura, Ko, Farzin, Farzin, Mufti, Ghulam J. and Guinn, Barbara-Anne (2009) Anti-tumour immunity in a model of acute myeloid leukaemia. Leukemia and Lymphoma, 50 (3), 447-454. (doi:10.1080/10428190802653776).

Record type: Article

Abstract

Whole-cell vaccines allow the induction of anti-tumor immune responses without the need to define tumor antigens. We wished to directly compare, for the first time, the capacity of B7-1, B7-2 and 4-1BB ligand (4-1BBL) costimulatory molecules to convert murine and human acute myeloid leukemia (AML) cells into whole vaccines. 32Dc-kit is a murine myeloid cell line, which develops an AML-like disease over a protracted period, emulating human AML disease development. 32Dc-kit cells were modified to express elevated levels of B7-1, B7-2 or 4-1BBL, and each led to tumor rejection, although only mice injected with 32Dc-kit/B7-2 cells were able to reject subsequent parental tumor cell challenge. T-cell deficient nude mice were able to reject the 32Dc-kit variants, but they could not reject parental cell challenge; however, we found no evidence of cytotoxic T lymphocyte or natural killer (NK) activity ex vivo suggesting that tumor cell killing was mediated by an immune response that could not be recapitulated using purified NK or T cells as lone effectors. In human allogeneic mixed lymphocyte reactions (MLRs), we found no single costimulatory molecule was more effective, suggesting that the induction of a universal anti-tumor response will require a combination of ostimulatory molecules

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More information

Published date: March 2009
Keywords: costimulation, acute myeloid leukaemia, B7-1/CD80, B7-2/CD86, 4-1BB/CD137, immune gene therapy, whole cell vaccine, mouse, human, NK cells

Identifiers

Local EPrints ID: 69864
URI: https://eprints.soton.ac.uk/id/eprint/69864
ISSN: 1042-8194
PURE UUID: ebcfe390-00c4-4863-9182-17f82388f78f

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Date deposited: 08 Dec 2009
Last modified: 19 Jul 2017 00:05

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Contributors

Author: Adam T.C. Cheuk
Author: James W. Wells
Author: Lucas Chan
Author: Nigel B. Westwood
Author: Stuart A. Berger
Author: Hideo Yagita
Author: Ko Okumura
Author: Farzin Farzin
Author: Ghulam J. Mufti
Author: Barbara-Anne Guinn

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