Linked CD4 T cell help: broadening immune attack against cancer by vaccination
Linked CD4 T cell help: broadening immune attack against cancer by vaccination
In the last decade, immunotherapy with monoclonal antibodies targeting immunological check points has become a breakthrough therapeutic modality for solid cancers. However, only up to 50 % of patients benefit from this powerful approach. For others vaccination might provide a plausible addition or alternative. For induction of effective anticancer immunity CD4+ T cell help is required, which is often difficult to induce to self cancer targets because of tolerogenic mechanisms. Our approach for cancer vaccines has been to incorporate into the vaccine design sequences able to activate foreign T cell help, through genetically linking cancer targets to microbial sequences (King et al. in Nat Med 4(11):1281–1286, 1998; Savelyeva et al. in Nat Biotechnol 19(8):760–764, 2001). This harnesses the non-tolerized CD4 T cell repertoire available in patients to help induction of effective immunity against fused cancer antigens. Multiple immune effector mechanisms including antibody, CD8+ T cells as well as CD4 effector T cells can be activated using this strategy. Delivery via DNA vaccines has already indicated clinical efficacy. The same principle of linked T cell help has now been transferred to other novel vaccine modalities to further potentiate immunity against cancer targets.
Springer Berlin, Heidelberg
Savelyeva, Natalia
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Allen, Alex
acab9114-885e-4a11-b88d-163703629f80
Chotprakaitiat, Warayut
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Harden, Elena
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Jobsri, Jantipa
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Godeseth, Rosemary
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Wang, Yidao
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Stevenson, Freda
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Ottensmeier, Christian
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Savelyeva, Natalia
804c3e15-d260-4717-9b7c-15c16ba87fc7
Allen, Alex
acab9114-885e-4a11-b88d-163703629f80
Chotprakaitiat, Warayut
13d4f863-d75b-4891-bde1-74d0f4607369
Harden, Elena
25640c4c-e4f5-4558-86d5-a3f74c9c972e
Jobsri, Jantipa
fcffeef7-8d3e-4a78-a258-fb5502a01fba
Godeseth, Rosemary
ad04327f-06e5-449a-81e8-479d00790b8a
Wang, Yidao
34466a09-d91e-48e2-91db-3a39f6dffa8d
Stevenson, Freda
ba803747-c0ac-409f-a9c2-b61fde009f8c
Ottensmeier, Christian
42b8a398-baac-4843-a3d6-056225675797
Savelyeva, Natalia, Allen, Alex, Chotprakaitiat, Warayut, Harden, Elena, Jobsri, Jantipa, Godeseth, Rosemary, Wang, Yidao, Stevenson, Freda and Ottensmeier, Christian
(2016)
Linked CD4 T cell help: broadening immune attack against cancer by vaccination.
In,
Current Topics in Microbiology and Immunology.
Berlin, DE.
Springer Berlin, Heidelberg.
(doi:10.1007/82_2016_500).
Record type:
Book Section
Abstract
In the last decade, immunotherapy with monoclonal antibodies targeting immunological check points has become a breakthrough therapeutic modality for solid cancers. However, only up to 50 % of patients benefit from this powerful approach. For others vaccination might provide a plausible addition or alternative. For induction of effective anticancer immunity CD4+ T cell help is required, which is often difficult to induce to self cancer targets because of tolerogenic mechanisms. Our approach for cancer vaccines has been to incorporate into the vaccine design sequences able to activate foreign T cell help, through genetically linking cancer targets to microbial sequences (King et al. in Nat Med 4(11):1281–1286, 1998; Savelyeva et al. in Nat Biotechnol 19(8):760–764, 2001). This harnesses the non-tolerized CD4 T cell repertoire available in patients to help induction of effective immunity against fused cancer antigens. Multiple immune effector mechanisms including antibody, CD8+ T cells as well as CD4 effector T cells can be activated using this strategy. Delivery via DNA vaccines has already indicated clinical efficacy. The same principle of linked T cell help has now been transferred to other novel vaccine modalities to further potentiate immunity against cancer targets.
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Accepted/In Press date: September 2016
e-pub ahead of print date: 5 October 2016
Organisations:
Cancer Sciences
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Local EPrints ID: 401978
URI: http://eprints.soton.ac.uk/id/eprint/401978
PURE UUID: f8ab5d81-c299-407a-a039-005f1b9f9c5b
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Date deposited: 26 Oct 2016 12:46
Last modified: 16 Mar 2024 02:54
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Author:
Alex Allen
Author:
Warayut Chotprakaitiat
Author:
Elena Harden
Author:
Jantipa Jobsri
Author:
Rosemary Godeseth
Author:
Yidao Wang
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