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Title:
Autologous monocyte-derived DC vaccination combined with cisplatin in stage III and IV melanoma patients: a prospective, randomized phase 2 trial | Cancer Immunology, Immunotherapy
Description:
Background Autologous dendritic cell (DC) vaccines can induce tumor-specific T cells, but their effect can be counteracted by immunosuppressive mechanisms. Cisplatin has shown immunomodulatory effects in vivo which may enhance efficacy of DC vaccination. Methods This is a prospective, randomized, open-label phase 2 study (NCT02285413) including stage III and IV melanoma patients receiving 3 biweekly vaccinations of gp100 and tyrosinase mRNA-loaded monocyte-derived DCs with or without cisplatin. Primary objectives were to study immunogenicity and feasibility, and secondary objectives were to assess toxicity and survival. Results Twenty-two stage III and 32 stage IV melanoma patients were analyzed. Antigen-specific CD8+ T cells were found in 44% versus 67% and functional T cell responses in 28% versus 19% of skin-test infiltrating lymphocytes in patients receiving DC vaccination with and without cisplatin, respectively. Four patients stopped cisplatin because of toxicity and continued DC monotherapy. No therapy-related grade 3 or 4 adverse events occurred due to DC monotherapy. During combination therapy, one therapy-related grade 3 adverse event, decompensated heart failure due to fluid overload, occurred. The clinical outcome parameters did not clearly suggest significant differences. Conclusions Combination of DC vaccination and cisplatin in melanoma patients is feasible and safe, but does not seem to result in more tumor-specific T cell responses or improved clinical outcome, when compared to DC vaccination monotherapy.
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Keywords {🔍}
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Topics {✒️}
dendritic-cell based immunotherapy—focusing hla-dr−cd14+cd11b+cd33+ cells skin-test infiltrating lymphocytes autologous epstein–barr virus cis-dichlorodiammine-platinum versus dacarbazine formalin-fixed paraffin-embedded tumor-induced immune suppression skin-test infiltrating lymphocyte dendritic cell-based vaccination antibody-tsa complex removals ficoll-paque density centrifugation cd3+cd4+cd25+foxp3+ cells efficient antigen-presenting cells myeloid-derived suppressor cells dendritic cell immunotherapy tjitske duiveman-de boer autologous dc vaccines clinical-grade dendritic cells phorbol myristate acetate-stimulated conventional therapeutic interventions article download pdf antigen-specific t-cells anti-hla-dr-bv510 anti-hla-dr-pe sided log-rank test anti-tumor immune response anti-hla-abc-pe anti-hla-dq-pe effective anti-pd-1 mabs anna de goede common terminology criteria hla-type independent monitoring dc dendritic cell dendritic cell vaccination full access cisplatin-induced antitumor immunomodulation common adverse events keyhole limpet hemocyanin opal reagent incubations 5 ng/ml il-1β induce tumor-specific melanoma-related death frequent adverse events adverse events leading tumor antigen-specific autologous dc vaccination privacy choices/manage cookies primary antibody incubations phase ii study therapy-related grade 3
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headline:Autologous monocyte-derived DC vaccination combined with cisplatin in stage III and IV melanoma patients: a prospective, randomized phase 2 trial
description:Autologous dendritic cell (DC) vaccines can induce tumor-specific T cells, but their effect can be counteracted by immunosuppressive mechanisms. Cisplatin has shown immunomodulatory effects in vivo which may enhance efficacy of DC vaccination. This is a prospective, randomized, open-label phase 2 study (NCT02285413) including stage III and IV melanoma patients receiving 3 biweekly vaccinations of gp100 and tyrosinase mRNA-loaded monocyte-derived DCs with or without cisplatin. Primary objectives were to study immunogenicity and feasibility, and secondary objectives were to assess toxicity and survival. Twenty-two stage III and 32 stage IV melanoma patients were analyzed. Antigen-specific CD8+ T cells were found in 44% versus 67% and functional T cell responses in 28% versus 19% of skin-test infiltrating lymphocytes in patients receiving DC vaccination with and without cisplatin, respectively. Four patients stopped cisplatin because of toxicity and continued DC monotherapy. No therapy-related grade 3 or 4 adverse events occurred due to DC monotherapy. During combination therapy, one therapy-related grade 3 adverse event, decompensated heart failure due to fluid overload, occurred. The clinical outcome parameters did not clearly suggest significant differences. Combination of DC vaccination and cisplatin in melanoma patients is feasible and safe, but does not seem to result in more tumor-specific T cell responses or improved clinical outcome, when compared to DC vaccination monotherapy.
datePublished:2020-01-24T00:00:00Z
dateModified:2020-01-24T00:00:00Z
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keywords:
Dendritic cell
Vaccination
Cisplatin
Melanoma
Immunotherapy
Oncology
Immunology
Cancer Research
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headline:Autologous monocyte-derived DC vaccination combined with cisplatin in stage III and IV melanoma patients: a prospective, randomized phase 2 trial
description:Autologous dendritic cell (DC) vaccines can induce tumor-specific T cells, but their effect can be counteracted by immunosuppressive mechanisms. Cisplatin has shown immunomodulatory effects in vivo which may enhance efficacy of DC vaccination. This is a prospective, randomized, open-label phase 2 study (NCT02285413) including stage III and IV melanoma patients receiving 3 biweekly vaccinations of gp100 and tyrosinase mRNA-loaded monocyte-derived DCs with or without cisplatin. Primary objectives were to study immunogenicity and feasibility, and secondary objectives were to assess toxicity and survival. Twenty-two stage III and 32 stage IV melanoma patients were analyzed. Antigen-specific CD8+ T cells were found in 44% versus 67% and functional T cell responses in 28% versus 19% of skin-test infiltrating lymphocytes in patients receiving DC vaccination with and without cisplatin, respectively. Four patients stopped cisplatin because of toxicity and continued DC monotherapy. No therapy-related grade 3 or 4 adverse events occurred due to DC monotherapy. During combination therapy, one therapy-related grade 3 adverse event, decompensated heart failure due to fluid overload, occurred. The clinical outcome parameters did not clearly suggest significant differences. Combination of DC vaccination and cisplatin in melanoma patients is feasible and safe, but does not seem to result in more tumor-specific T cell responses or improved clinical outcome, when compared to DC vaccination monotherapy.
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Dendritic cell
Vaccination
Cisplatin
Melanoma
Immunotherapy
Oncology
Immunology
Cancer Research
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