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Severe adverse immunologic reaction in a patient with glioblastoma receiving autologous dendritic cell vaccines combined with GM-CSF and dose-intensified temozolomide.

Publication ,  Journal Article
Mitchell, DA; Sayour, EJ; Reap, E; Schmittling, R; DeLeon, G; Norberg, P; Desjardins, A; Friedman, AH; Friedman, HS; Archer, G; Sampson, JH
Published in: Cancer Immunol Res
April 2015

Therapeutic vaccination of patients with cancer-targeting tumor-associated antigens is a promising strategy for the specific eradication of invasive malignancies with minimal toxicity to normal tissues. However, as increasingly potent modalities for stimulating immunologic responses are developed for clinical evaluation, the risk of inflammatory and autoimmune toxicities also may be exacerbated. In this report, we describe the induction of a severe (grade 3) immunologic reaction in a patient with newly diagnosed glioblastoma (GBM) receiving autologous RNA-pulsed dendritic cell (DC) vaccines admixed with GM-CSF and administered coordinately with cycles of dose-intensified temozolomide. Shortly after the eighth administration of the admixed intradermal vaccine, the patient experienced dizziness, flushing, conjunctivitis, headache, and the outbreak of a disseminated macular/papular rash and bilateral indurated injection sites. Immunologic workup of patient reactivity revealed sensitization to the GM-CSF component of the vaccine and the production of high levels of anti-GM-CSF autoantibodies during vaccination. Removal of GM-CSF from the DC vaccine allowed continued vaccination without incident. Despite the known lymphodepletive and immunosuppressive effects of temozolomide, these observations demonstrate the capacity for the generation of severe immunologic reactivity in patients with GBM receiving DC-based therapy during adjuvant dose-intensified temozolomide.

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Published In

Cancer Immunol Res

DOI

EISSN

2326-6074

Publication Date

April 2015

Volume

3

Issue

4

Start / End Page

320 / 325

Location

United States

Related Subject Headings

  • Temozolomide
  • Middle Aged
  • Male
  • Humans
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Glioblastoma
  • Dendritic Cells
  • Dacarbazine
  • Combined Modality Therapy
  • Cancer Vaccines
 

Citation

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Mitchell, D. A., Sayour, E. J., Reap, E., Schmittling, R., DeLeon, G., Norberg, P., … Sampson, J. H. (2015). Severe adverse immunologic reaction in a patient with glioblastoma receiving autologous dendritic cell vaccines combined with GM-CSF and dose-intensified temozolomide. Cancer Immunol Res, 3(4), 320–325. https://doi.org/10.1158/2326-6066.CIR-14-0100
Mitchell, Duane A., Elias J. Sayour, Elizabeth Reap, Robert Schmittling, Gabriel DeLeon, Pamela Norberg, Annick Desjardins, et al. “Severe adverse immunologic reaction in a patient with glioblastoma receiving autologous dendritic cell vaccines combined with GM-CSF and dose-intensified temozolomide.Cancer Immunol Res 3, no. 4 (April 2015): 320–25. https://doi.org/10.1158/2326-6066.CIR-14-0100.
Mitchell DA, Sayour EJ, Reap E, Schmittling R, DeLeon G, Norberg P, et al. Severe adverse immunologic reaction in a patient with glioblastoma receiving autologous dendritic cell vaccines combined with GM-CSF and dose-intensified temozolomide. Cancer Immunol Res. 2015 Apr;3(4):320–5.
Mitchell, Duane A., et al. “Severe adverse immunologic reaction in a patient with glioblastoma receiving autologous dendritic cell vaccines combined with GM-CSF and dose-intensified temozolomide.Cancer Immunol Res, vol. 3, no. 4, Apr. 2015, pp. 320–25. Pubmed, doi:10.1158/2326-6066.CIR-14-0100.
Mitchell DA, Sayour EJ, Reap E, Schmittling R, DeLeon G, Norberg P, Desjardins A, Friedman AH, Friedman HS, Archer G, Sampson JH. Severe adverse immunologic reaction in a patient with glioblastoma receiving autologous dendritic cell vaccines combined with GM-CSF and dose-intensified temozolomide. Cancer Immunol Res. 2015 Apr;3(4):320–325.

Published In

Cancer Immunol Res

DOI

EISSN

2326-6074

Publication Date

April 2015

Volume

3

Issue

4

Start / End Page

320 / 325

Location

United States

Related Subject Headings

  • Temozolomide
  • Middle Aged
  • Male
  • Humans
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Glioblastoma
  • Dendritic Cells
  • Dacarbazine
  • Combined Modality Therapy
  • Cancer Vaccines