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    Prostate Ca immunotherapy induces T-cell response


    The study analyzed Th cells and CTLs from 14 men with hormone-sensitive or metastatic castration-resistant prostate cancer who were treated with sipuleucel-T in clinical trials. Peripheral blood mononuclear cells isolated from the patients and from healthy donors as controls were cultured with PA2024, the fusion antigen conjugating human prostatic acid phosphatase (PAP) with human granulocyte-macrophage colony-stimulating factor, or PAP by itself. Flow cytometry was used to quantify antigen-specific proliferation of the immune cells, and cell-surface CD107a expression was measured to assess CTL lytic activity.

    The correlation between overall survival and CTL activity in the sipuleucel-T-treated patients was investigated using Pearson’s correlation that showed a statistically significant relationship between longer survival and normalized CTL activity at 26 weeks post-treatment for both PAP- and PA2024-specific cells.

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    In addition, with patients divided into two groups based on whether their antigen-specific CTL activity was above or below the median CTL response, Kaplan-Meier analysis showed overall survival was significantly longer in the group of men with the better antigen-specific CTL response.

    Looking ahead, Dr. Drake suggested that the assays used in this study might be applied to research for developing combination regimens for enhancing benefit of sipuleucel-T.

    “Perhaps they could be used to evaluate which combinations induce the best immune response. In addition, it is possible that the assays might be used to identify patients whose T-cell response to sipuleucel-T is waning and thereby select men who might benefit from another dose of sipuleucel-T in the same manner as we administer a booster vaccine for infectious diseases.”

    Several of Dr. Drake’s co-authors have a financial or other relationship with or are employees of Dendreon. For a full list of disclosures, click here.

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