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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

Patel, Poulam M., Ottensmeier, Christian H., Mulatero, Clive, Lorigan, Paul, Plummer, Ruth, Pandha, Hardev, Elsheikh, Somaia, Hadjimichael, Efthymios, Villasanti, Naty, Adams, Sally E. , 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, 7 (6), e1433516. e1433516-1-e1433516-15.

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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.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Patel, Poulam M.
Ottensmeier, Christian H.
Mulatero, Clive
Lorigan, Paul
Plummer, Ruth
Pandha, HardevH.Pandha@surrey.ac.uk
Elsheikh, Somaia
Hadjimichael, Efthymios
Villasanti, Naty
Adams, Sally E.
Cunnell, Michelle
Metheringham, Rachael L.
Brentville, Victoria A.
Machado, Lee
Daniels, Ian
Gijon, Mohamed
Hannaman, Drew
Durrant, Lindy G.
Date : 22 February 2018
DOI : 10.1080/2162402X.2018.1433516
Copyright Disclaimer : © 2018 The Author(s). Published with license by Taylor & Francis Group, LLC © Poulam M. Patel, Christian H. Ottensmeier, Clive Mulatero, Paul Lorigan, Ruth Plummer, Hardev Pandha, Somaia Elsheikh, Efthymios Hadjimichael, Naty Villasanti, Michelle Cunnell, Rachael L. Metheringham, Victoria A. Brentville, Lee Machado, Ian Daniels, Mohamed Gijon, Drew Hannaman and Lindy G. Durrant
Uncontrolled Keywords : Immunotherapy; Vaccine; Melanoma; T-cell
Depositing User : Clive Harris
Date Deposited : 09 Jul 2018 09:31
Last Modified : 23 Feb 2019 02:08
URI: http://epubs.surrey.ac.uk/id/eprint/848670

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