A plant expressed conjugate vaccine breaks CD4
tolerance and induces potent immunity against
metastatic Her2+ breast cancer
A plant expressed conjugate vaccine breaks CD4
tolerance and induces potent immunity against
metastatic Her2+ breast cancer
Passive antibody therapy for cancer is an effective but costly treatment modality. Induction of therapeutically potent anti-cancer antibodies by active vaccination is an attractive alternative but has proven challenging in cancer due to tolerogenic pressure in patients. Here we used the clinically relevant cancer target Her2, known to be susceptible to targeting by antibody therapy, to demonstrate how potent antibody can be induced by vaccination. A novel 44kD Her2 protein fragment was generated and found to be highly effective at inducing anti-Her2 antibody including trastuzumab-like reactivities. In the tolerant and spontaneous BALB-neuT mouse model of metastatic breast cancer this Her2-targeting vaccine was only effective if the fragment was conjugated to a foreign immunogenic carrier; Fragment C of tetanus toxin. Only the conjugate vaccine induced high affinity anti-Her2 antibody of multiple isotypes and suppressed tumour development. The magnitude of CD4 T-cell help and breadth of cytokines secreted by the CD4 T helper cells induced to the foreign antigen was critical. We used a highly efficient plant-based bio-manufacturing process for protein antigens, magnICON, for vaccine expression, to underpin feasibility of future clinical testing. Hence our novel Her2-targeting conjugate vaccine combines preclinical efficacy with clinical deliverability, thus setting the scene for therapeutic testing.
Chotprakaikiat, Warayut
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Allen, Alex
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Bui-Minh, Duc
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Harden, Elena
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Jobsric, Jantipa
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Cavallo, Federica
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Gleba, Yuri
a7bf0d0e-77f2-4faf-86c0-7fa58e55ffd1
Stevenson, Freda
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Ottensmeier, Christian
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Klimyu, Victor
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Savelyeva, Natalia
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June 2016
Chotprakaikiat, Warayut
de230391-cf32-4aa9-a8de-eb1293ae75aa
Allen, Alex
acab9114-885e-4a11-b88d-163703629f80
Bui-Minh, Duc
00747042-d05c-48ed-87fb-3f4943dd74e7
Harden, Elena
25640c4c-e4f5-4558-86d5-a3f74c9c972e
Jobsric, Jantipa
fdc759a5-dde5-48c3-bd94-15d08b4fc020
Cavallo, Federica
30ba60ca-541b-418e-bf63-e030b8600a78
Gleba, Yuri
a7bf0d0e-77f2-4faf-86c0-7fa58e55ffd1
Stevenson, Freda
ba803747-c0ac-409f-a9c2-b61fde009f8c
Ottensmeier, Christian
42b8a398-baac-4843-a3d6-056225675797
Klimyu, Victor
495b7360-5350-4470-b063-55179cea5ebb
Savelyeva, Natalia
804c3e15-d260-4717-9b7c-15c16ba87fc7
Chotprakaikiat, Warayut, Allen, Alex, Bui-Minh, Duc, Harden, Elena, Jobsric, Jantipa, Cavallo, Federica, Gleba, Yuri, Stevenson, Freda, Ottensmeier, Christian, Klimyu, Victor and Savelyeva, Natalia
(2016)
A plant expressed conjugate vaccine breaks CD4
tolerance and induces potent immunity against
metastatic Her2+ breast cancer.
OncoImmunology, 5 (6), [e1166323].
(doi:10.1080/2162402X.2016.1166323).
Abstract
Passive antibody therapy for cancer is an effective but costly treatment modality. Induction of therapeutically potent anti-cancer antibodies by active vaccination is an attractive alternative but has proven challenging in cancer due to tolerogenic pressure in patients. Here we used the clinically relevant cancer target Her2, known to be susceptible to targeting by antibody therapy, to demonstrate how potent antibody can be induced by vaccination. A novel 44kD Her2 protein fragment was generated and found to be highly effective at inducing anti-Her2 antibody including trastuzumab-like reactivities. In the tolerant and spontaneous BALB-neuT mouse model of metastatic breast cancer this Her2-targeting vaccine was only effective if the fragment was conjugated to a foreign immunogenic carrier; Fragment C of tetanus toxin. Only the conjugate vaccine induced high affinity anti-Her2 antibody of multiple isotypes and suppressed tumour development. The magnitude of CD4 T-cell help and breadth of cytokines secreted by the CD4 T helper cells induced to the foreign antigen was critical. We used a highly efficient plant-based bio-manufacturing process for protein antigens, magnICON, for vaccine expression, to underpin feasibility of future clinical testing. Hence our novel Her2-targeting conjugate vaccine combines preclinical efficacy with clinical deliverability, thus setting the scene for therapeutic testing.
Text
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More information
Accepted/In Press date: 11 March 2016
e-pub ahead of print date: 9 June 2016
Published date: June 2016
Organisations:
Cancer Sciences
Identifiers
Local EPrints ID: 393542
URI: http://eprints.soton.ac.uk/id/eprint/393542
ISSN: 2162-402X
PURE UUID: 5c69d015-a3be-4642-903c-ebd1fcd5527d
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Date deposited: 06 May 2016 15:54
Last modified: 15 Mar 2024 05:32
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Contributors
Author:
Warayut Chotprakaikiat
Author:
Alex Allen
Author:
Duc Bui-Minh
Author:
Elena Harden
Author:
Jantipa Jobsric
Author:
Federica Cavallo
Author:
Yuri Gleba
Author:
Victor Klimyu
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