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.

Autor:	Patel PM; Academic Department of Clinical Oncology, Division of Cancer & Stem Cells, University of Nottingham, Nottingham, UK., Ottensmeier CH; Southampton Experimental Cancer Medicine Centre and Southampton University Hospitals, Faculty of Medicine, Southampton, UK., Mulatero C; St James's University Hospital, Leeds, UK., Lorigan P; Institute of Cancer Sciences, University of Manchester, The Christie NHS Foundation Trust, Manchester, UK., Plummer R; Northern Institute for Cancer Research, Medical School, University of Newcastle-upon-Tyne and Wear, UK., Pandha H; Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK., Elsheikh S; University of Nottingham, School of Medicine Queen's Medical Centre, Nottingham, UK., Hadjimichael E; University of Nottingham, School of Medicine Queen's Medical Centre, Nottingham, UK., Villasanti N; University of Nottingham, School of Medicine Queen's Medical Centre, Nottingham, UK., Adams SE; Scancell Limited, Academic Department of Clinical Oncology, University of Nottingham, Nottingham, UK., Cunnell M; Academic Department of Clinical Oncology, Division of Cancer & Stem Cells, University of Nottingham, Nottingham, UK., Metheringham RL; Scancell Limited, Academic Department of Clinical Oncology, University of Nottingham, Nottingham, UK., Brentville VA; Scancell Limited, Academic Department of Clinical Oncology, University of Nottingham, Nottingham, UK., Machado L; Scancell Limited, Academic Department of Clinical Oncology, University of Nottingham, Nottingham, UK., Daniels I; Scancell Limited, Academic Department of Clinical Oncology, University of Nottingham, Nottingham, UK., Gijon M; Scancell Limited, Academic Department of Clinical Oncology, University of Nottingham, Nottingham, UK., Hannaman D; Ichor Medical Systems, Inc., San Diego, CA, USA., Durrant LG; Academic Department of Clinical Oncology, Division of Cancer & Stem Cells, University of Nottingham, Nottingham, UK.; Scancell Limited, Academic Department of Clinical Oncology, University of Nottingham, Nottingham, UK.
Jazyk:	angličtina
Zdroj:	Oncoimmunology [Oncoimmunology] 2018 Feb 22; Vol. 7 (6), pp. e1433516. Date of Electronic Publication: 2018 Feb 22 (Print Publication: 2018).
DOI:	10.1080/2162402X.2018.1433516
Abstrakt:	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.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu