Ctim-27. Doc1021 Cell-based Vaccination as Adjuvant Therapy for Glioblastoma: Phase I Clinical Trial Analysis
Year: 2024
Type: conference-abstract
Abstract: Glioblastoma is an aggressive tumor for which median survival remains 14-18 months despite aggressive standard of care. Cellular immunotherapy approaches have recently shown promise. Homologous antigenic loading is an ex-vivo technique that leverages p38MAPK and mTORC1 signaling cascades to initiate powerful cDC1-like skewing in monocyte-derived dendritic cells, leading to downstream induction of tissue-infiltrating, cytolytic effector memory T-cells. This open-label phase I clinical trial evaluated the autologous dendritic cell vaccine DOC1021 prepared through homologous antigenic loading and administered bilaterally near the deep cervical lymph nodes. Three courses of vaccine were administered every 2 weeks after completion of chemoradiation, adjuvanted concurrently with six weeks of weekly type I interferon. Four dose levels from 3.5x106 to 3.6x107 total vaccine cells were tested. Tumor progression prior to vaccination was not an exclusion criterion. Sixteen newly diagnosed IDH-WT patients completed treatment, median age 63 years and 94% MGMTp unmethylated. The most common related AEs were grade 1 injection-site reactions and grade 1-3 fatigue and urticaria. No DLTs were observed. Immunohistochemistry of tumors derived from early post-vaccination second resections showed enhanced CD8+ T-cell infiltration and pathologic findings consistent with residual rather than relapsed GBM in 2/3 patients. Analysis of post-vaccination PBMC in dose level cohorts 2-4 indicated expansion of both CD4+ (13/13) and CD8+ (11/13) central memory T-cell compartments (p<0.002 and p<0.05, respectively) as well as expansion of CD8+CD127+ T-cells (12/13; p<0.001). Among three patients for whom tissue was obtained pre- and post-vaccination, clinical outcomes correlated with Visium spatial transcriptomic analysis. Median survival for the MGMTp unmethylated cohort (n=15) has not yet been reached but is statistically greater (p<0.05) than that of matched historic controls. The results indicate that DOC1021 is safe, can be effectively integrated within existing standards of care and is potentially efficacious in a challenging patient population.
Source: Neuro-Oncology
Authors: Yoshua Esquenazi, Jay Zhu, Sigmund Hsu, Rodrick Zvavanjanja, Mia Vu, Eva Highberg, Trivedi Akshar, Wei Liu, Madhuri Namekar, Colby Hofferek, James Ernste, Corey Mossop, Clay Christina, Sabina Amin, Musher Benjamin, Vinod Ravi, Kemnade Jan, Laura Aguilar, Alan Turtz, Nitin Tandon, Vanaja Konduri, Joseph Georges, William Decker
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4404237644