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Analysis of DC vaccines used for phase II clinical trial in prostate carcinoma patients

ABSTRACT: Dendritic cell (DC)-based cancer vaccines are a promising immunotherapy against cancer. However, despite the vast number of clinical trials conducted so far, factors and manufacturing procedures essential for these therapeutics to induce effective anti-tumor immune responses have yet to be fully characterized. Here, we performed an extensive characterization of DCs used to vaccinate 18 prostate carcinoma patients enrolled in a pilot trial of TCR gamma alternate reading frame protein (TARP) peptide vaccination (NCT00908258) and looked for correlates with clinical and immunological responses. DCs showing lower expression of tolerogenic gene signature induced strong antigen-specific immune response and slowing in Prostate Specific Antigen (PSA) velocity, a surrogate for clinical response. These DCs were also characterized by lower surface expression of CD14, secretion of IL-10 and MCP-1; and greater secretion of MDC. When combined, these four factors were able to remarkably discriminate DCs that were sufficiently potent to induce strong immunological response. In summary, we identified DC factors essential for the activation of immune responses associated with TARP vaccination in prostate cancer patients. This study highlights the importance of in-depth characterization of DC vaccines – and other cellular therapies, to understand the critical factors that hinder potency and potential efficacy in patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE85698 | GEO | 2017/07/10

SECONDARY ACCESSION(S): PRJNA339129

REPOSITORIES: GEO

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