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Dendritic Cells Enhance Polyfunctionality of Adoptively Transferred T Cells That Target Cytomegalovirus in Glioblastoma.

Publication ,  Journal Article
Reap, EA; Suryadevara, CM; Batich, KA; Sanchez-Perez, L; Archer, GE; Schmittling, RJ; Norberg, PK; Herndon, JE; Healy, P; Congdon, KL; Yi, JS ...
Published in: Cancer Res
January 1, 2018

Median survival for glioblastoma (GBM) remains <15 months. Human cytomegalovirus (CMV) antigens have been identified in GBM but not normal brain, providing an unparalleled opportunity to subvert CMV antigens as tumor-specific immunotherapy targets. A recent trial in recurrent GBM patients demonstrated the potential clinical benefit of adoptive T-cell therapy (ATCT) of CMV phosphoprotein 65 (pp65)-specific T cells. However, ex vivo analyses from this study found no change in the capacity of CMV pp65-specific T cells to gain multiple effector functions or polyfunctionality, which has been associated with superior antitumor efficacy. Previous studies have shown that dendritic cells (DC) could further enhance tumor-specific CD8+ T-cell polyfunctionality in vivo when administered as a vaccine. Therefore, we hypothesized that vaccination with CMV pp65 RNA-loaded DCs would enhance the frequency of polyfunctional CMV pp65-specific CD8+ T cells after ATCT. Here, we report prospective results of a pilot trial in which 22 patients with newly diagnosed GBM were initially enrolled, of which 17 patients were randomized to receive CMV pp65-specific T cells with CMV-DC vaccination (CMV-ATCT-DC) or saline (CMV-ATCT-saline). Patients who received CMV-ATCT-DC vaccination experienced a significant increase in the overall frequencies of IFNγ+, TNFα+, and CCL3+ polyfunctional, CMV-specific CD8+ T cells. These increases in polyfunctional CMV-specific CD8+ T cells correlated (R = 0.7371, P = 0.0369) with overall survival, although we cannot conclude this was causally related. Our data implicate polyfunctional T-cell responses as a potential biomarker for effective antitumor immunotherapy and support a formal assessment of this combination approach in a larger randomized study.Significance: A randomized pilot trial in patients with GBM implicates polyfunctional T-cell responses as a biomarker for effective antitumor immunotherapy. Cancer Res; 78(1); 256-64. ©2017 AACR.

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Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

January 1, 2018

Volume

78

Issue

1

Start / End Page

256 / 264

Location

United States

Related Subject Headings

  • Viral Matrix Proteins
  • Treatment Outcome
  • T-Lymphocytes
  • Phosphoproteins
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Immunotherapy, Adoptive
  • Humans
  • Glioblastoma
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Reap, E. A., Suryadevara, C. M., Batich, K. A., Sanchez-Perez, L., Archer, G. E., Schmittling, R. J., … Sampson, J. H. (2018). Dendritic Cells Enhance Polyfunctionality of Adoptively Transferred T Cells That Target Cytomegalovirus in Glioblastoma. Cancer Res, 78(1), 256–264. https://doi.org/10.1158/0008-5472.CAN-17-0469
Reap, Elizabeth A., Carter M. Suryadevara, Kristen A. Batich, Luis Sanchez-Perez, Gary E. Archer, Robert J. Schmittling, Pamela K. Norberg, et al. “Dendritic Cells Enhance Polyfunctionality of Adoptively Transferred T Cells That Target Cytomegalovirus in Glioblastoma.Cancer Res 78, no. 1 (January 1, 2018): 256–64. https://doi.org/10.1158/0008-5472.CAN-17-0469.
Reap EA, Suryadevara CM, Batich KA, Sanchez-Perez L, Archer GE, Schmittling RJ, et al. Dendritic Cells Enhance Polyfunctionality of Adoptively Transferred T Cells That Target Cytomegalovirus in Glioblastoma. Cancer Res. 2018 Jan 1;78(1):256–64.
Reap, Elizabeth A., et al. “Dendritic Cells Enhance Polyfunctionality of Adoptively Transferred T Cells That Target Cytomegalovirus in Glioblastoma.Cancer Res, vol. 78, no. 1, Jan. 2018, pp. 256–64. Pubmed, doi:10.1158/0008-5472.CAN-17-0469.
Reap EA, Suryadevara CM, Batich KA, Sanchez-Perez L, Archer GE, Schmittling RJ, Norberg PK, Herndon JE, Healy P, Congdon KL, Gedeon PC, Campbell OC, Swartz AM, Riccione KA, Yi JS, Hossain-Ibrahim MK, Saraswathula A, Nair SK, Dunn-Pirio AM, Broome TM, Weinhold KJ, Desjardins A, Vlahovic G, McLendon RE, Friedman AH, Friedman HS, Bigner DD, Fecci PE, Mitchell DA, Sampson JH. Dendritic Cells Enhance Polyfunctionality of Adoptively Transferred T Cells That Target Cytomegalovirus in Glioblastoma. Cancer Res. 2018 Jan 1;78(1):256–264.

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

January 1, 2018

Volume

78

Issue

1

Start / End Page

256 / 264

Location

United States

Related Subject Headings

  • Viral Matrix Proteins
  • Treatment Outcome
  • T-Lymphocytes
  • Phosphoproteins
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Immunotherapy, Adoptive
  • Humans
  • Glioblastoma