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

    Research output: Contribution to conference typesAbstractResearch

    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

    Conference

    Conference15th International Conference on Progress in Vaccination Against Cancer (PIVAC-15)
    Period6/10/15 → …
    Internet address

    Fingerprint

    DNA Vaccines
    Dendritic Cells
    Melanoma
    Vaccines
    Clinical Trials
    Recurrence
    Epitopes
    T-Lymphocytes
    gp100 Melanoma Antigen
    Survival
    Cross-Priming
    Melanoma-Specific Antigens
    T-Lymphocyte Epitopes
    Electroporation
    Antibodies
    Neoplasms
    Therapeutics
    Immunoglobulin G
    Neoplasm Metastasis

    Cite this

    Durrant, L. G., Ottensmeier, C. H., Mulatero, C., Lorigan, P., Plummer, R., Cunnell, M., ... 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), .
    Durrant, L G ; Ottensmeier, C H ; Mulatero, C ; Lorigan, P ; Plummer, R ; Cunnell, M ; Metheringham, R ; Brentville, V ; Machado, Lee ; Daniels, I ; Hannaman, D ; Patel, P M. / 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), .
    @conference{9d097413bcf6435a95daf456f3a27b7e,
    title = "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 = "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.",
    author = "Durrant, {L G} and Ottensmeier, {C H} and C Mulatero and P Lorigan and R Plummer and M Cunnell and R Metheringham and V Brentville and Lee Machado and I Daniels and D Hannaman and Patel, {P M}",
    year = "2015",
    month = "10",
    day = "6",
    language = "English",
    note = "15th International Conference on Progress in Vaccination Against Cancer (PIVAC-15) ; Conference date: 06-10-2015",
    url = "https://www.scancell.co.uk/file-manager/scientific-papers/pivac-15-programme.pdf",

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    Durrant, LG, Ottensmeier, CH, Mulatero, C, Lorigan, P, Plummer, R, Cunnell, M, Metheringham, R, Brentville, V, Machado, L, Daniels, I, Hannaman, D & Patel, PM 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?' 15th International Conference on Progress in Vaccination Against Cancer (PIVAC-15), 6/10/15, .

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

    2015. Abstract from 15th International Conference on Progress in Vaccination Against Cancer (PIVAC-15), .

    Research output: Contribution to conference typesAbstractResearch

    TY - CONF

    T1 - 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?

    AU - Durrant, L G

    AU - Ottensmeier, C H

    AU - Mulatero, C

    AU - Lorigan, P

    AU - Plummer, R

    AU - Cunnell, M

    AU - Metheringham, R

    AU - Brentville, V

    AU - Machado, Lee

    AU - Daniels, I

    AU - Hannaman, D

    AU - Patel, P M

    PY - 2015/10/6

    Y1 - 2015/10/6

    N2 - 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.

    AB - 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.

    UR - https://www.scancell.co.uk/file-manager/scientific-papers/pivac-15-programme.pdf

    M3 - Abstract

    ER -

    Durrant LG, Ottensmeier CH, Mulatero C, Lorigan P, Plummer R, Cunnell M et al. 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?. 2015. Abstract from 15th International Conference on Progress in Vaccination Against Cancer (PIVAC-15), .