Poster Presentation 18th International Symposium on Dendritic Cells 2026

Tetanus toxoid preconditioning enhances dendritic cell vaccine migration and patient survival in glioblastoma clinical trials: experience with ATTAC and the validation ELEVATE study (#271)

Sarah L Cook 1 , Tarek Bou Dargham 1 , Pamela Norberg 1 , Gary E Archer 1 , Luis Sanchez-Perez 1 , Weihua Xie 1 , Kendra L Congdon 1 , Aditya Mohan 1 , Kelly M Hotchkiss 1 , Arezoo Beig Parikhani 1 , Gloria Broadwater 1 , James E Herndon II 1 , Margaret O Johnson 1 , Henry S Friedman 1 , Katherine B Peters 1 , Annick Desjardins 1 , Mustafa Khasraw 1 , David Ashley 1 , John H Sampson 2 , Kristen Batich Vaios 1
  1. Duke University School of Medicine, Durham, NC, United States
  2. University of Colorado School of Medicine, Aurora, Colorado, USA

BACKGROUND: The ATTAC trial (NCT00639639) was a small, randomized DC vaccine trial wherein 12 patients with newly diagnosed glioblastoma received autologous DC vaccines pulsed with Cytomegalovirus (CMV) pp65 RNA integrated with standard of care adjuvant temozolomide (TMZ). ATTAC revealed that pre-conditioning the vaccine site with tetanus-diphtheria toxoid (Td) significantly increased DC migration to vaccine site-draining lymph nodes and resulted in superior progression-free and overall survival (PFS/OS). Herein, we describe the ELEVATE validation trial (NCT02366728) to evaluate the impact of Td pre-conditioning on DC migration, immune makeup, and clinical outcomes in a larger sample size.

METHODS: This was a double-blinded trial of 52 patients randomized to Td versus unpulsed DC pre-conditioning prior to the fourth pp65-DC vaccine. DC migration was assessed using SPECT-CT of 111Indium-labeled DCs. Immune monitoring of NK cells, T cells, and pp65-specific T cells was conducted at various timepoints. PFS and OS were calculated.

RESULTS: Of the 52 patients, 43 were evaluable for the DC migration endpoint. In the intention-to-treat population, 3 patients (11%) in the Td cohort experienced grade 1 adverse events (AEs), and 2 patients (7%) experienced grade 2 AEs. No grade 3 or 4 AEs occurred, and no AEs occurred in the control cohort. DC migration was significantly increased at 24 and 48 hours post-vaccination for the Td cohort compared to control (p=0.03). Patient peripheral T cells were reduced as a result of TMZ administration which corresponded with reduced CMV-specific T cell numbers. Surprisingly, NK cells increased with TMZ treatment, suggesting TMZ may affect innate and adaptive immunity differently. Td pre-conditioning again resulted in improved median OS (20 mths versus 16.5 mths) and exceptional long-term survivors, where no long-term survivors occurred in the unpulsed DC cohort.

CONCLUSION: Enhancing peripheral DC migration in glioblastoma can augment clinical outcomes despite standard of care-induced T cell decline.