A clinical trial of a DNA vaccine (SCIB1) that targets dendritic cells in vivo in fully resected melanoma patients; a vaccine to prevent disease recurrence?

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

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Abstract

Background: SCIB1 is a DNA vaccine encoding a human IgG1 antibody with CDRs that contain four epitopes from two melanoma antigens (three from gp100 and one from TRP2). The vaccine elicits potent anti-tumour responses by stimulating high frequency, high avidity T-cells via both direct and cross-presentation of antibody. A clinical study in stage III/IV melanoma patients, all with tumour present at study entry, showed that 2-8mg doses could induce T-cell responses in 7/9 patients with no associated toxicity. Encouragingly overall survival was 31 months. This study addresses the question as to whether SCIB1 can be used as an adjuvant therapy in fully resected melanoma patients to prevent further disease. Methods: Sixteen patients with fully resected stage III (n=9) or stage IV (n=7) melanoma were immunised with 4mg of SCIB1 by intramuscular electroporation at 3 weekly intervals and subsequently at 3 and 6 months. Patients could continue treatment for 5 years. Results: All 16 patients showed vaccine-epitope-specific T-cell responses (i.e. proliferation ex vivo and/or γIFN Elispot responses in-vitro). Twelve patients responded to all four epitopes, two patients to three epitopes, one to two epitopes and one to a single epitope. Five patients remain in the continuation phase - all show strong T-cell memory responses following boosting. At present, median survival time is 37 months from trial entry and 41.5 months from diagnosis of metastases. Overall survival is 100% for both groups. Five patients relapsed at 1, 4, 14, 17 and 18 months but have shown no further recurrences at follow-up. Conclusion: These results show that a DNA vaccine encoding epitopes from melanoma antigens can induce measurable T-cell responses and, furthermore, it may confer protection from recurrence of melanoma with little associated toxicity. SCIB1 deserves further evaluation as an adjuvant therapy.
Original languageEnglish
Publication statusPublished - 6 Oct 2015
Event15th International Conference on Progress in Vaccination Against Cancer (PIVAC-15) - Tübingen, Germany
Duration: 6 Oct 2015 → …
https://www.scancell.co.uk/file-manager/scientific-papers/pivac-15-programme.pdf

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Conference15th International Conference on Progress in Vaccination Against Cancer (PIVAC-15)
Period6/10/15 → …
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Durrant, L. G., Ottensmeier, C. H., Mulatero, C., Lorigan, P., Plummer, R., Cunnell, M., Metheringham, R., Brentville, V., Machado, L., Daniels, I., Hannaman, D., & Patel, P. M. (2015). A clinical trial of a DNA vaccine (SCIB1) that targets dendritic cells in vivo in fully resected melanoma patients; a vaccine to prevent disease recurrence?. Abstract from 15th International Conference on Progress in Vaccination Against Cancer (PIVAC-15), .