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Recognition and killing of autologous, primary glioblastoma tumor cells by human cytomegalovirus pp65-specific cytotoxic T cells.

Publication ,  Journal Article
Nair, SK; De Leon, G; Boczkowski, D; Schmittling, R; Xie, W; Staats, J; Liu, R; Johnson, LA; Weinhold, K; Archer, GE; Sampson, JH; Mitchell, DA
Published in: Clin Cancer Res
May 15, 2014

PURPOSE: Despite aggressive conventional therapy, glioblastoma (GBM) remains uniformly lethal. Immunotherapy, in which the immune system is harnessed to specifically attack malignant cells, offers a treatment option with less toxicity. The expression of cytomegalovirus (CMV) antigens in GBM presents a unique opportunity to target these viral proteins for tumor immunotherapy. Although the presence of CMV within malignant gliomas has been confirmed by several laboratories, its relevance as an immunologic target in GBM has yet to be established. The objective of this study was to explore whether T cells stimulated by CMV pp65 RNA-transfected dendritic cells (DC) target and eliminate autologous GBM tumor cells in an antigen-specific manner. EXPERIMENTAL DESIGN: T cells from patients with GBM were stimulated with autologous DCs pulsed with CMV pp65 RNA, and the function of the effector CMV pp65-specific T cells was measured. RESULTS: In this study, we demonstrate the ability to elicit CMV pp65-specific immune responses in vitro using RNA-pulsed autologous DCs generated from patients with newly diagnosed GBM. Importantly, CMV pp65-specific T cells lyse autologous, primary GBM tumor cells in an antigen-specific manner. Moreover, T cells expanded in vitro using DCs pulsed with total tumor RNA demonstrated a 10- to 20-fold expansion of CMV pp65-specific T cells as assessed by tetramer analysis and recognition and killing of CMV pp65-expressing target cells. CONCLUSION: These data collectively demonstrate that CMV-specific T cells can effectively target glioblastoma tumor cells for immunologic killing and support the rationale for the development of CMV-directed immunotherapy in patients with GBM.

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Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

May 15, 2014

Volume

20

Issue

10

Start / End Page

2684 / 2694

Location

United States

Related Subject Headings

  • Young Adult
  • Viral Matrix Proteins
  • Tumor Cells, Cultured
  • T-Lymphocytes, Cytotoxic
  • T-Lymphocytes
  • RNA, Viral
  • Phosphoproteins
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Nair, S. K., De Leon, G., Boczkowski, D., Schmittling, R., Xie, W., Staats, J., … Mitchell, D. A. (2014). Recognition and killing of autologous, primary glioblastoma tumor cells by human cytomegalovirus pp65-specific cytotoxic T cells. Clin Cancer Res, 20(10), 2684–2694. https://doi.org/10.1158/1078-0432.CCR-13-3268
Nair, Smita K., Gabriel De Leon, David Boczkowski, Robert Schmittling, Weihua Xie, Janet Staats, Rebecca Liu, et al. “Recognition and killing of autologous, primary glioblastoma tumor cells by human cytomegalovirus pp65-specific cytotoxic T cells.Clin Cancer Res 20, no. 10 (May 15, 2014): 2684–94. https://doi.org/10.1158/1078-0432.CCR-13-3268.
Nair SK, De Leon G, Boczkowski D, Schmittling R, Xie W, Staats J, et al. Recognition and killing of autologous, primary glioblastoma tumor cells by human cytomegalovirus pp65-specific cytotoxic T cells. Clin Cancer Res. 2014 May 15;20(10):2684–94.
Nair, Smita K., et al. “Recognition and killing of autologous, primary glioblastoma tumor cells by human cytomegalovirus pp65-specific cytotoxic T cells.Clin Cancer Res, vol. 20, no. 10, May 2014, pp. 2684–94. Pubmed, doi:10.1158/1078-0432.CCR-13-3268.
Nair SK, De Leon G, Boczkowski D, Schmittling R, Xie W, Staats J, Liu R, Johnson LA, Weinhold K, Archer GE, Sampson JH, Mitchell DA. Recognition and killing of autologous, primary glioblastoma tumor cells by human cytomegalovirus pp65-specific cytotoxic T cells. Clin Cancer Res. 2014 May 15;20(10):2684–2694.

Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

May 15, 2014

Volume

20

Issue

10

Start / End Page

2684 / 2694

Location

United States

Related Subject Headings

  • Young Adult
  • Viral Matrix Proteins
  • Tumor Cells, Cultured
  • T-Lymphocytes, Cytotoxic
  • T-Lymphocytes
  • RNA, Viral
  • Phosphoproteins
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male