Posts in Category: Product - SCIB1

Targeting gp100 and TRP-2 with a DNA vaccine

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

Poulam M. Patel, Christian H. Ottensmeier, Clive Mulatero, Paul Lorigan, Ruth Plummer, Hardev Pandha, Somaia Elsheikh, Efthymios Hadjimichael, Naty Villasanti, Sally E. Adams, Michelle Cunnell, Rachael L. Metheringham, Victoria A. Brentville, Lee Machado, Ian Daniels, Mohamed Gijon, Drew Hannaman and Lindy G. Durrant

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 (ρ < 0.01). In contrast, patients with tumor showed a significantly higher response to the 8 mg dose than the 4 mg dose (ρ < 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 (ρ = 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.

SCIB1 combined with PD-1 blockade induced efficient therapy of poorly immunogenic tumors (2016)

SCIB1 combined with PD-1 blockade induced efficient therapy of poorly immunogenic tumors (2016)

Wei Xue, Victoria A. Brentville, Peter Symonds, Katherine W. Cook, Hideo Yagita, Rachael L. Metheringham and Lindy G. Durrant

ABSTRACT:

Purpose: We have previously shown that supraoptimal signaling of high avidity T cells leads to high expression of PD-1 and inhibition of proliferation. This study was designed to see if this effect could be mitigated by combining a vaccine that stimulates high avidity T cells with PD-1 blockade.

Experimental Design: We investigated the anti-tumor effect of a huIgG1 antibody DNA vaccine (SCIB1) and PD-1 blockade.

Results: Vaccination of HLA-DR4 transgenic mice with SCIB1 induced high frequency and avidity T cell responses that resulted in survival (40%) of mice with established B16F1-DR4 tumors. SCIB1 vaccination was associated with increased infiltration of CD4 and CD8 T cells within the tumor but was also associated with upregulation of PD-L1 within the tumor environment. PD-1 blockade also resulted in increased CD8 T cell infiltration and an anti-tumor response with 50% of mice showing long term survival.In line with our hypothesis that PD-1/PD-L1 signaling results in inhibition of proliferation of high avidity T cells at the tumor site, the combination of PD-1 blockade with vaccination, enhanced the number and proliferation of the CD8 tumor infiltrate. This resulted in a potent anti-tumor response with 80% survival of the mice.

Conclusions: There is a benefit in combining PD-1 blockade with vaccines that induce high avidity T cell responses and in particular with SCIB1.

Progress in Vaccination against Cancer 2016

PIVAC 2016 SCIB1 Clinical Trial Poster

L.G. Durrant, C. Ottensmeier, C. Mulatero, P. Lorigan, R. Plummer, R. Metheringham, V.Brentville, S. Adams, L. Machado, I. Daniels, D. Hannaman and P.M. Patel 

PIVAC 2016 Adjuvants for Moditope Poster

Katherine Cook, Peter Symonds, Victoria Brentville, Rachael Metheringham,  Wei Xue and Lindy Durrant

PIVAC 2016 Citrullinated Alpha Enolase Poster

K. Cook, I. Daniels, V. Brentville, R. Metheringham, W. Xue, P. Symonds, T. Pitt, M.Gijon and L. Durrant

PIVAC 2016 Protein Arginine Deiminase Enzymes Poster

R. Metheringham, M. Gijon, I. Daniels, K. Cook, P. Symonds, T. Pitt, W. Xue, V. Brentville and L. Durrant

Progress in Vaccination against Cancer 2015

PIVAC 2015 SCIB2 Poster

Wei Xue, Rachael Metheringham, Victoria Brentville, Katherine Cook, Peter Symonds, Ian Daniel and Lindy Durrant

PIVAC 2015 Moditope poster 2

V. Brentville, W. Xue, P. Symonds, K. Cook, B. Gunn, R. Metheringham and L.G. Durrant

PIVAC 2015 SCIB1 resected disease

L.G. Durrant, C. Ottensmeier, C. Mulatero, P. Lorigan, R. Plummer, R. Metheringham, V. Brentville, L. Machado, I. Daniels, D. Hannaman and P.M. Patel

PIVAC 2015 SCIB1 plus checkpoint inhibition

Wei Xue, Victoria Brentville, Rachael Metheringham, Katherine Cook, Peter, Symonds, Ian Daniels and Lindy Durrant