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NY-ESO-1 specific antibody and cellular responses in melanoma patients primed with NY-ESO-1 protein in ISCOMATRIX and boosted with recombinant NY-ESO-1 fowlpox virus

NY-ESO-1 specific antibody and cellular responses in melanoma patients primed with NY-ESO-1 protein in ISCOMATRIX and boosted with recombinant NY-ESO-1 fowlpox virus
NY-ESO-1 specific antibody and cellular responses in melanoma patients primed with NY-ESO-1 protein in ISCOMATRIX and boosted with recombinant NY-ESO-1 fowlpox virus
Vaccination strategies based on repeated injections of NY-ESO-1 protein formulated in ISCOMATRIX particles (NY-ESO-1 ISCOMATRIX) have shown to elicit combined NY-ESO-1 specific antibody and T cell responses. However, it remains unclear whether heterologous prime-boost strategies based on the combination with NY-ESO-1 ISCOMATRIX with different NY-ESO-1 boosting reagents could be used to increase NY-ESO-1 CD8+ or CD4+ T cell responses. To address this question, we carried out a randomized clinical trial in 39 high-risk, resected melanoma patients vaccinated with NY-ESO-1 ISCOMATRIX, and then boosted with repeated injections of either recombinant fowlpox virus encoding full length NY-ESO-1 (rF-NY-ESO-1) (Arm A) or NY-ESO-1 ISCOMATRIX alone (Arm B). We have comprehensively analyzed NY-ESO-1 specific T cells and B cells response in all patients before and after vaccination for a total of seven time points per patient. NY-ESO-1 ISCOMATRIX alone elicited a strong NY-ESO-1 specific CD4+ T cell and antibody response, which was maintained by both regiments at similar levels. However, CD8+ T cell responses were significantly boosted in 3 out of 18 patients in Arm A after the first rF-NY-ESO-1 injection and such responses were maintained until the end of the trial, while no patients in Arm B showed similar CD8+ T cell responses. In addition, our results clearly identified immunodominant regions in the NY-ESO-1 protein: NY-ESO-179–102 and NY-ESO-1115–138 for CD4+ T cells and NY-ESO-185–108 for CD8+ T cells in a large proportion of vaccinated patients. These regions of NY-ESO-1 protein should be considered in future clinical trials as immunodominant epitopes.
cancer vaccines, NY-ESO-1, ISCOMATRIX, fowlpox
0020-7136
E590-E601
Chen, Ji-Li
4fcaef6a-e7d4-4c47-8fb9-1e0387a4a5c6
Dawoodji, Amina
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Tarlton, Andrea
4ac9547e-74dc-4213-8836-56fb1bafe196
Gnjatic, Sacha
e8d38145-f42f-4db4-9dda-c998c46013df
Tajar, Abdelouahid
fb5a5ad6-ddca-4ff3-8649-b00e208f9254
Karydis, Ioannis
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Browning, Judy
ffc429c0-069e-43d7-9244-fcdf02c878e1
Pratap, Sarah
1cc385c1-cb14-486b-832c-1af6938b8aa2
Verfaille, Christian
314093ec-2925-48da-8b50-2ed66fff0f5f
Venhaus, Ralph R.
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Pan, Linda
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Altman, Douglas G.
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Cebon, Jonathan S.
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Old, Lloyd L.
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Nathan, Paul
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Ottensmeier, Christian
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Middleton, Mark
554291fb-66be-4f4b-8e3c-c3352b5ad6f3
Cerundolo, Vincenzo
813bcd4a-ca19-48a3-86e4-71d131e2065a
Chen, Ji-Li
4fcaef6a-e7d4-4c47-8fb9-1e0387a4a5c6
Dawoodji, Amina
c25cb8f7-e9a4-4087-8320-c1869d17aeaa
Tarlton, Andrea
4ac9547e-74dc-4213-8836-56fb1bafe196
Gnjatic, Sacha
e8d38145-f42f-4db4-9dda-c998c46013df
Tajar, Abdelouahid
fb5a5ad6-ddca-4ff3-8649-b00e208f9254
Karydis, Ioannis
95a2388c-7165-40e1-8b73-87234caea36d
Browning, Judy
ffc429c0-069e-43d7-9244-fcdf02c878e1
Pratap, Sarah
1cc385c1-cb14-486b-832c-1af6938b8aa2
Verfaille, Christian
314093ec-2925-48da-8b50-2ed66fff0f5f
Venhaus, Ralph R.
5f90fb0e-d70c-44e3-9b98-f5b95046f293
Pan, Linda
5ce3b1ae-8af7-4e08-b25a-f6f3a29cd2b7
Altman, Douglas G.
f0d739a4-dc94-44d1-a497-603a3ed7d7e6
Cebon, Jonathan S.
8e66ccf1-1ce2-4253-b84b-798b773e607b
Old, Lloyd L.
6f579ffa-7545-4d7b-b56f-2efe9a3da096
Nathan, Paul
f2d9a686-efbf-448c-a31a-e7b84aee3593
Ottensmeier, Christian
42b8a398-baac-4843-a3d6-056225675797
Middleton, Mark
554291fb-66be-4f4b-8e3c-c3352b5ad6f3
Cerundolo, Vincenzo
813bcd4a-ca19-48a3-86e4-71d131e2065a

Chen, Ji-Li, Dawoodji, Amina, Tarlton, Andrea, Gnjatic, Sacha, Tajar, Abdelouahid, Karydis, Ioannis, Browning, Judy, Pratap, Sarah, Verfaille, Christian, Venhaus, Ralph R., Pan, Linda, Altman, Douglas G., Cebon, Jonathan S., Old, Lloyd L., Nathan, Paul, Ottensmeier, Christian, Middleton, Mark and Cerundolo, Vincenzo (2015) NY-ESO-1 specific antibody and cellular responses in melanoma patients primed with NY-ESO-1 protein in ISCOMATRIX and boosted with recombinant NY-ESO-1 fowlpox virus. International Journal of Cancer, 136 (6), E590-E601. (doi:10.1002/ijc.29118). (PMID:25081390)

Record type: Article

Abstract

Vaccination strategies based on repeated injections of NY-ESO-1 protein formulated in ISCOMATRIX particles (NY-ESO-1 ISCOMATRIX) have shown to elicit combined NY-ESO-1 specific antibody and T cell responses. However, it remains unclear whether heterologous prime-boost strategies based on the combination with NY-ESO-1 ISCOMATRIX with different NY-ESO-1 boosting reagents could be used to increase NY-ESO-1 CD8+ or CD4+ T cell responses. To address this question, we carried out a randomized clinical trial in 39 high-risk, resected melanoma patients vaccinated with NY-ESO-1 ISCOMATRIX, and then boosted with repeated injections of either recombinant fowlpox virus encoding full length NY-ESO-1 (rF-NY-ESO-1) (Arm A) or NY-ESO-1 ISCOMATRIX alone (Arm B). We have comprehensively analyzed NY-ESO-1 specific T cells and B cells response in all patients before and after vaccination for a total of seven time points per patient. NY-ESO-1 ISCOMATRIX alone elicited a strong NY-ESO-1 specific CD4+ T cell and antibody response, which was maintained by both regiments at similar levels. However, CD8+ T cell responses were significantly boosted in 3 out of 18 patients in Arm A after the first rF-NY-ESO-1 injection and such responses were maintained until the end of the trial, while no patients in Arm B showed similar CD8+ T cell responses. In addition, our results clearly identified immunodominant regions in the NY-ESO-1 protein: NY-ESO-179–102 and NY-ESO-1115–138 for CD4+ T cells and NY-ESO-185–108 for CD8+ T cells in a large proportion of vaccinated patients. These regions of NY-ESO-1 protein should be considered in future clinical trials as immunodominant epitopes.

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More information

Accepted/In Press date: 14 July 2014
e-pub ahead of print date: 14 August 2014
Published date: 15 March 2015
Keywords: cancer vaccines, NY-ESO-1, ISCOMATRIX, fowlpox
Organisations: Southampton Cancer Research UK Centre

Identifiers

Local EPrints ID: 396158
URI: https://eprints.soton.ac.uk/id/eprint/396158
ISSN: 0020-7136
PURE UUID: 0ab931ec-7e1e-44db-ae0f-46733119379e

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Date deposited: 31 May 2016 14:40
Last modified: 03 Aug 2018 16:34

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Contributors

Author: Ji-Li Chen
Author: Amina Dawoodji
Author: Andrea Tarlton
Author: Sacha Gnjatic
Author: Abdelouahid Tajar
Author: Ioannis Karydis
Author: Judy Browning
Author: Sarah Pratap
Author: Christian Verfaille
Author: Ralph R. Venhaus
Author: Linda Pan
Author: Douglas G. Altman
Author: Jonathan S. Cebon
Author: Lloyd L. Old
Author: Paul Nathan
Author: Mark Middleton
Author: Vincenzo Cerundolo

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