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Immunotherapies for Brain Cancer: From Preclinical Models to Human Trials

  • Thomas J. Wilson
  • Marianela Candolfi
  • Hikmat Assi
  • Mariela Moreno Ayala
  • Yohei Mineharu
  • Shawn L. Hervey-Jumper
  • Pedro R. Lowenstein
  • Maria G. Castro
Chapter
Part of the Tumors of the Central Nervous System book series (TCNS, volume 13)

Abstract

Glioblastoma Multiforme (GBM) is the most common and aggressive primary brain tumor. Every year ~22,000 patients are diagnosed with GBM in the US, and less than 5% survive 5 years post-diagnosis. Thus, novel therapeutic approaches are urgently needed to improve the outcome in these patients. Immunotherapy has the potential of stimulating the immune system to eliminate GBM cells that might have spread throughout the brain. Here we will discuss the latest advances in preclinical immunotherapy for glioma, which involve the local delivery of pro-inflammatory cytokines, such as Flt3L, Type I IFNs, IL-2, IL-4, and IL-12 using gene therapy vectors and neural stem cells, or the blockade of immune-suppressive mediators such as TGF-beta, FasL and phosphorylated STAT3. Novel immunotherapeutic approaches have also been assessed in clinical trials implemented in GBM patients. These involve the systemic or local adoptive transfer of autologous immune cells activated ex vivo back into the patient, and the administration of dendritic cell vaccines loaded with tumor peptides or cells, which induce active immunity against GBM. Preclinical and clinical findings so far indicate that immunotherapy improves anti-tumor immunity in preclinical GBM models and patients, which makes it a valuable adjuvant in the treatment of GBM.

Keywords

Malignant Glioma Glioblastoma Multiforme Anaplastic Astrocytoma Antitumor Immunity Methylated MGMT Promoter 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

This work was supported by National Institutes of Health/National Institute of Neurological Disorders & Stroke (NIH/NINDS) Grants 1UO1-NS052465, UO1-NS052465-04S1, 1RO1-NS074387 and 1RO1-NS 057711 to M.G.C.; NIH/NINDS Grants 1R21-NS 084275 and 1RO1- NS 061107 to P.R.L. T32 NS 007222, T32 CA 009676, T32 GM 007863, UL1TR000433; and the Department of Neurosurgery, University of Michigan School of Medicine. M.C. and M.M.A. were supported by the National Council of Science and Technology (CONICET, Argentina) PIP CONICET 114-201101-00353. We are grateful to Dr. K. Murasko for her academic leadership and M. Dahlgren, D. Tomford and S. Napolitan for superb administrative support.

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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Thomas J. Wilson
    • 1
  • Marianela Candolfi
    • 2
  • Hikmat Assi
    • 3
  • Mariela Moreno Ayala
    • 4
    • 5
  • Yohei Mineharu
    • 3
  • Shawn L. Hervey-Jumper
    • 1
  • Pedro R. Lowenstein
    • 3
  • Maria G. Castro
    • 3
  1. 1.Department of Neurosurgery, School of MedicineUniversity of MichiganAnn ArborUSA
  2. 2.Instituto de Investigaciones BiomédicasINBIOMED, Facultad de Medicina, Universidad de Buenos AiresBuenos AiresArgentina
  3. 3.Department of Neurosurgery, Department of Cell and Developmental Biology, School of MedicineUniversity of MichiganAnn ArborUSA
  4. 4.Instituto de Investigaciones BiomédicasNational Council of Science and Technology – University of Buenos AiresBuenos AiresArgentina
  5. 5.University of Buenos Aires School of MedicineBuenos AiresArgentina

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