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

Al's Comment:

 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.  


Posted on: 05/05/2020

(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.

 


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