Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA339129 | ENA |
REPOSITORIES: ENA
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Project description: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.
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Project description:Patients with high-risk localized prostate cancer (tumor-node-metastasis ≥ T2b or prostate-specific antigen ≥ 15 ng/mL or Gleason glade ≥ 4+3) were enrolled into a phase II clinical trial of neoadjuvant chemotherapy with docetaxel and mitoxantrone followed by prostatectomy. Pretreatment prostate tissue was acquired by needle biopsy and posttreatment tissue was acquired by prostatectomy. Prostate epithelium was captured by microdissection, and transcript levels were quantitated by cDNA microarray hybridization. To evaluate gene expression alterations after chemotherapy, neoplastic epithelium from pretreated biopsy and posttreated prostatectomy specimens were laser captured separately (∼3,000 cells per sample). cDNA synthesized from amplified total RNA of pre-treated biopsy samples and post-treatment surgical samples were hybridized head-to-head, alternating Cy3 and Cy5 to custom-made microarrays composed of 6,200 clones derived from the Prostate Expression Database.
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