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Improved Survival for GBM Patients Treated with DC Vaccine and Adjuvant TLR-3 Agonist in Phase II Clinical Trial

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  • Improved Survival for GBM Patients Treated with DC Vaccine and Adjuvant TLR-3 Agonist in Phase II Clinical Trial

    (Abstract from 2020 AANS Annual Meeting)
    441: Improved Survival for GBM Patients Treated with DC Vaccine and Adjuvant TLR-3 Agonist in Phase II Clinical
    Trial
    Rosenblum-Mahaley Clinical Research Award
    Joseph Paul Antonios, MD (New Haven, CT); Richard Everson; Aaron Mochizuki; Sara Khattab; Prashant Romiyo;
    Matthew Sun; Diana Moughon; William Yong; Anthony Wang; Timothy Cloughesy; Robert Prins; Linda Liau
    Introduction: We and others have documented immune responses following dendritic cell (DC) vaccination as an active
    immunotherapeutic treatment for these patients. In this Phase II clinical trial, we randomized malignant glioma patients to
    receive autologous tumor lysate pulsed DC vaccination with and without adjuvant toll-like receptor (TLR) agonists. TLRs
    are present on dendritic cells and serve to modulate immune responses.
    Methods: Twenty-three patients with WHO grade III or IV glioma were treated with three intradermal injections of
    autologous tumor lysate-pulsed DC on days 0, 14, and 28 followed by an adjuvant placebo, TLR-7 agonist (Resiquimod),
    or TLR-3 agonist (Poly ICLC). Mass cytometry (CyTOF) was used to analyze immune cell populations of patient peripheral
    blood mononuclear cells (PBMC) before and following treatment. Single cell RNA sequencing (scRNseq) gene expression
    analysis of systemic PBMCs was utilized to determine functional significance of adjuvant administration.
    Results: DC-vaccinated patients that received adjuvant Poly ICLC treatment had a significantly improved median survival
    of 54 months over placebo (11 months) and adjuvant Resiquimod (17 months) groups (P<0.01). scRNA seq analysis
    demonstrated increased immune cell activation and expression of proinflammatory genes, as well as peripheral myeloid
    cell population expansion that was associated with increased survival.
    Conclusion: Overall, these findings suggest that adjuvant Poly ICLC treatment improves outcomes with autologous
    lysate-pulsed DC vaccine treatment via modulation of pro-inflammatory pathways.

  • #2
    Al Musella's Comments: (This is his personal views and are not necessarily the views of the Musella Foundation!)

    This is a small randomized trial. and included grade 3 as well as grade 4 brain tumors but the results are very impressive, by adding an immune stimulant, (which is approved for skin cancer) which is applied topically. Reports median survival of 54 months compared to 11 months for placebo.

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    • #3
      Sadly, nobody can get access to polyICLC? Am I right?

      Comment


      • #4
        It is still experimental. We are looking into getting access but it doesn't look possible

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