Skip to main content
Journal cover image

Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients.

Publication ,  Journal Article
Mitchell, DA; Batich, KA; Gunn, MD; Huang, M-N; Sanchez-Perez, L; Nair, SK; Congdon, KL; Reap, EA; Archer, GE; Desjardins, A; Friedman, AH ...
Published in: Nature
March 19, 2015

After stimulation, dendritic cells (DCs) mature and migrate to draining lymph nodes to induce immune responses. As such, autologous DCs generated ex vivo have been pulsed with tumour antigens and injected back into patients as immunotherapy. While DC vaccines have shown limited promise in the treatment of patients with advanced cancers including glioblastoma, the factors dictating DC vaccine efficacy remain poorly understood. Here we show that pre-conditioning the vaccine site with a potent recall antigen such as tetanus/diphtheria (Td) toxoid can significantly improve the lymph node homing and efficacy of tumour-antigen-specific DCs. To assess the effect of vaccine site pre-conditioning in humans, we randomized patients with glioblastoma to pre-conditioning with either mature DCs or Td unilaterally before bilateral vaccination with DCs pulsed with Cytomegalovirus phosphoprotein 65 (pp65) RNA. We and other laboratories have shown that pp65 is expressed in more than 90% of glioblastoma specimens but not in surrounding normal brain, providing an unparalleled opportunity to subvert this viral protein as a tumour-specific target. Patients given Td had enhanced DC migration bilaterally and significantly improved survival. In mice, Td pre-conditioning also enhanced bilateral DC migration and suppressed tumour growth in a manner dependent on the chemokine CCL3. Our clinical studies and corroborating investigations in mice suggest that pre-conditioning with a potent recall antigen may represent a viable strategy to improve anti-tumour immunotherapy.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

March 19, 2015

Volume

519

Issue

7543

Start / End Page

366 / 369

Location

England

Related Subject Headings

  • Viral Matrix Proteins
  • Treatment Outcome
  • Tetanus Toxoid
  • Survival Rate
  • Substrate Specificity
  • Phosphoproteins
  • Mice, Inbred C57BL
  • Mice
  • Lymph Nodes
  • Immunotherapy
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Mitchell, D. A., Batich, K. A., Gunn, M. D., Huang, M.-N., Sanchez-Perez, L., Nair, S. K., … Sampson, J. H. (2015). Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients. Nature, 519(7543), 366–369. https://doi.org/10.1038/nature14320
Mitchell, Duane A., Kristen A. Batich, Michael D. Gunn, Min-Nung Huang, Luis Sanchez-Perez, Smita K. Nair, Kendra L. Congdon, et al. “Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients.Nature 519, no. 7543 (March 19, 2015): 366–69. https://doi.org/10.1038/nature14320.
Mitchell DA, Batich KA, Gunn MD, Huang M-N, Sanchez-Perez L, Nair SK, et al. Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients. Nature. 2015 Mar 19;519(7543):366–9.
Mitchell, Duane A., et al. “Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients.Nature, vol. 519, no. 7543, Mar. 2015, pp. 366–69. Pubmed, doi:10.1038/nature14320.
Mitchell DA, Batich KA, Gunn MD, Huang M-N, Sanchez-Perez L, Nair SK, Congdon KL, Reap EA, Archer GE, Desjardins A, Friedman AH, Friedman HS, Herndon JE, Coan A, McLendon RE, Reardon DA, Vredenburgh JJ, Bigner DD, Sampson JH. Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients. Nature. 2015 Mar 19;519(7543):366–369.
Journal cover image

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

March 19, 2015

Volume

519

Issue

7543

Start / End Page

366 / 369

Location

England

Related Subject Headings

  • Viral Matrix Proteins
  • Treatment Outcome
  • Tetanus Toxoid
  • Survival Rate
  • Substrate Specificity
  • Phosphoproteins
  • Mice, Inbred C57BL
  • Mice
  • Lymph Nodes
  • Immunotherapy