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Massive clonal expansion of medulloblastoma-specific T cells during adoptive cellular therapy.

Publication ,  Journal Article
Flores, C; Wildes, T; Dean, BD; Moore, G; Drake, J; Abraham, R; Gil, J; Yegorov, O; Yang, C; Dean, J; Moneypenny, C; Shin, D; Pham, C ...
Published in: Sci Adv
November 2019

In both human and murine systems, we have developed an adoptive cellular therapy platform against medulloblastoma and glioblastoma that uses dendritic cells pulsed with a tumor RNA transcriptome to expand polyclonal tumor-reactive T cells against a plurality of antigens within heterogeneous brain tumors. We demonstrate that peripheral TCR Vβ repertoire analysis after adoptive cellular therapy reveals that effective response to adoptive cellular therapy is concordant with massive in vivo expansion and persistence of tumor-specific T cell clones within the peripheral blood. In preclinical models of medulloblastoma and glioblastoma, and in a patient with relapsed medulloblastoma receiving adoptive cellular therapy, an early and massive expansion of tumor-reactive lymphocytes, coupled with prolonged persistence in the peripheral blood, is observed during effective therapeutic response to immunotherapy treatment.

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Published In

Sci Adv

DOI

EISSN

2375-2548

Publication Date

November 2019

Volume

5

Issue

11

Start / End Page

eaav9879

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Receptors, Antigen, T-Cell, alpha-beta
  • Mice, Transgenic
  • Mice
  • Medulloblastoma
  • Immunotherapy, Adoptive
  • Humans
  • Cerebellar Neoplasms
  • Cell Line, Tumor
  • Animals
 

Citation

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Flores, C., Wildes, T., Dean, B. D., Moore, G., Drake, J., Abraham, R., … Mitchell, D. (2019). Massive clonal expansion of medulloblastoma-specific T cells during adoptive cellular therapy. Sci Adv, 5(11), eaav9879. https://doi.org/10.1126/sciadv.aav9879
Flores, C., T. Wildes, B DiVita Dean, G. Moore, J. Drake, R. Abraham, J. Gil, et al. “Massive clonal expansion of medulloblastoma-specific T cells during adoptive cellular therapy.Sci Adv 5, no. 11 (November 2019): eaav9879. https://doi.org/10.1126/sciadv.aav9879.
Flores C, Wildes T, Dean BD, Moore G, Drake J, Abraham R, et al. Massive clonal expansion of medulloblastoma-specific T cells during adoptive cellular therapy. Sci Adv. 2019 Nov;5(11):eaav9879.
Flores, C., et al. “Massive clonal expansion of medulloblastoma-specific T cells during adoptive cellular therapy.Sci Adv, vol. 5, no. 11, Nov. 2019, p. eaav9879. Pubmed, doi:10.1126/sciadv.aav9879.
Flores C, Wildes T, Dean BD, Moore G, Drake J, Abraham R, Gil J, Yegorov O, Yang C, Dean J, Moneypenny C, Shin D, Pham C, Krauser J, King J, Grant G, Driscoll T, Kurtzberg J, McLendon R, Gururangan S, Mitchell D. Massive clonal expansion of medulloblastoma-specific T cells during adoptive cellular therapy. Sci Adv. 2019 Nov;5(11):eaav9879.

Published In

Sci Adv

DOI

EISSN

2375-2548

Publication Date

November 2019

Volume

5

Issue

11

Start / End Page

eaav9879

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Receptors, Antigen, T-Cell, alpha-beta
  • Mice, Transgenic
  • Mice
  • Medulloblastoma
  • Immunotherapy, Adoptive
  • Humans
  • Cerebellar Neoplasms
  • Cell Line, Tumor
  • Animals