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Targeting gp100 and TRP-2 with a DNA vaccine: Incorporating T cell epitopes with a human IgG1 antibody induces potent T cell responses that are associated with favourable clinical outcome in a phase I/II trial

Targeting gp100 and TRP-2 with a DNA vaccine: Incorporating T cell epitopes with a human IgG1 antibody induces potent T cell responses that are associated with favourable clinical outcome in a phase I/II trial
Targeting gp100 and TRP-2 with a DNA vaccine: Incorporating T cell epitopes with a human IgG1 antibody induces potent T cell responses that are associated with favourable clinical outcome in a phase I/II trial
A DNA vaccine, SCIB1, incorporating two CD8 and two CD4 epitopes from TRP-2/gp100 was evaluated in patients with metastatic melanoma. Each patient received SCIB1 via intramuscular injection with electroporation. The trial was designed to find the safest dose of SCIB1 which induced immune/clinical responses in patients with or without tumour. Fifteen patients with tumor received SCIB1 doses of 0.4-8 mg whilst 20 fully-resected patients received 2–8 mg doses. Twelve patients elected to continue immunization every 3 months for up to 39 months. SCIB1 induced dose-dependent T cell responses in 88% of patients with no serious adverse effects or dose limiting toxicities. The intensity of the T cell responses was significantly higher in patients receiving 4 mg doses without tumor when compared to those with tumor (p < 0.01). In contrast, patients with tumor showed a significantly higher response to the 8 mg dose than the 4 mg dose (p < 0.03) but there was no significant difference in the patients without tumor. One of 15 patients with measurable disease showed an objective tumor response and 7/15 showed stable disease. 5/20 fully-resected patients have experienced disease recurrence but all remained alive at the cut-off date with a median observation time of 37 months. A positive clinical outcome was associated with MHC-I and MHC-II expression on tumors prior to therapy (p = 0.027).We conclude that SCIB1 is well tolerated and stimulates potent T cell responses in melanoma patients. It deserves further evaluation as a single agent adjuvant therapy or in combination with checkpoint inhibitors in advanced disease.
2162-402X
Patel, Poulam M.
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Ottensmeier, Christian H.
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Mulatero, Clive
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Lorigan, Paul
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Plummer, Ruth
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Pandha, Hardev
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Elsheikh, Somaia
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Hadjimichael, Efthymios
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Villasanti, Naty
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Cunnell, Michelle
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Metheringham, Rachael L.
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Brentville, Victoria A.
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Machado, Lee
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Daniels, Ian
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Gijon, Mohamed
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Hannaman, Drew
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Durrant, Lindy G.
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Patel, Poulam M.
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Ottensmeier, Christian H.
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Mulatero, Clive
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Lorigan, Paul
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Plummer, Ruth
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Pandha, Hardev
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Elsheikh, Somaia
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Hadjimichael, Efthymios
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Villasanti, Naty
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Cunnell, Michelle
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Metheringham, Rachael L.
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Brentville, Victoria A.
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Machado, Lee
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Daniels, Ian
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Gijon, Mohamed
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Hannaman, Drew
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Durrant, Lindy G.
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Patel, Poulam M., Ottensmeier, Christian H., Mulatero, Clive, Lorigan, Paul, Plummer, Ruth, Pandha, Hardev, Elsheikh, Somaia, Hadjimichael, Efthymios, Villasanti, Naty, Cunnell, Michelle, Metheringham, Rachael L., Brentville, Victoria A., Machado, Lee, Daniels, Ian, Gijon, Mohamed, Hannaman, Drew and Durrant, Lindy G. (2018) Targeting gp100 and TRP-2 with a DNA vaccine: Incorporating T cell epitopes with a human IgG1 antibody induces potent T cell responses that are associated with favourable clinical outcome in a phase I/II trial. OncoImmunology. (doi:10.1080/2162402X.2018.1433516).

Record type: Article

Abstract

A DNA vaccine, SCIB1, incorporating two CD8 and two CD4 epitopes from TRP-2/gp100 was evaluated in patients with metastatic melanoma. Each patient received SCIB1 via intramuscular injection with electroporation. The trial was designed to find the safest dose of SCIB1 which induced immune/clinical responses in patients with or without tumour. Fifteen patients with tumor received SCIB1 doses of 0.4-8 mg whilst 20 fully-resected patients received 2–8 mg doses. Twelve patients elected to continue immunization every 3 months for up to 39 months. SCIB1 induced dose-dependent T cell responses in 88% of patients with no serious adverse effects or dose limiting toxicities. The intensity of the T cell responses was significantly higher in patients receiving 4 mg doses without tumor when compared to those with tumor (p < 0.01). In contrast, patients with tumor showed a significantly higher response to the 8 mg dose than the 4 mg dose (p < 0.03) but there was no significant difference in the patients without tumor. One of 15 patients with measurable disease showed an objective tumor response and 7/15 showed stable disease. 5/20 fully-resected patients have experienced disease recurrence but all remained alive at the cut-off date with a median observation time of 37 months. A positive clinical outcome was associated with MHC-I and MHC-II expression on tumors prior to therapy (p = 0.027).We conclude that SCIB1 is well tolerated and stimulates potent T cell responses in melanoma patients. It deserves further evaluation as a single agent adjuvant therapy or in combination with checkpoint inhibitors in advanced disease.

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Accepted/In Press date: 22 January 2018
e-pub ahead of print date: 22 February 2018

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Local EPrints ID: 420635
URI: https://eprints.soton.ac.uk/id/eprint/420635
ISSN: 2162-402X
PURE UUID: cbe049e3-10a6-46cf-8ee6-d5d0a6164be8

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Date deposited: 11 May 2018 16:30
Last modified: 19 Jul 2019 17:16

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Contributors

Author: Poulam M. Patel
Author: Clive Mulatero
Author: Paul Lorigan
Author: Ruth Plummer
Author: Hardev Pandha
Author: Somaia Elsheikh
Author: Efthymios Hadjimichael
Author: Naty Villasanti
Author: Michelle Cunnell
Author: Rachael L. Metheringham
Author: Victoria A. Brentville
Author: Lee Machado
Author: Ian Daniels
Author: Mohamed Gijon
Author: Drew Hannaman
Author: Lindy G. Durrant

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