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

dc.contributor.author

Flores, C

dc.contributor.author

Wildes, T

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Dean, B DiVita

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Moore, G

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Drake, J

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Abraham, R

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Gil, J

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Yegorov, O

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Yang, C

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Dean, J

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Moneypenny, C

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Shin, D

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Pham, C

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Krauser, J

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King, J

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Grant, G

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Driscoll, T

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Kurtzberg, J

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McLendon, R

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Gururangan, S

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Mitchell, D

dc.date.accessioned

2022-03-23T15:06:51Z

dc.date.available

2022-03-23T15:06:51Z

dc.date.issued

2019-11-27

dc.date.updated

2022-03-23T15:06:51Z

dc.description.abstract

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.

dc.identifier

aav9879

dc.identifier.issn

2375-2548

dc.identifier.issn

2375-2548

dc.identifier.uri

https://hdl.handle.net/10161/24571

dc.language

eng

dc.publisher

American Association for the Advancement of Science (AAAS)

dc.relation.ispartof

Science advances

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10.1126/sciadv.aav9879

dc.subject

T-Lymphocytes

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Cell Line, Tumor

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Animals

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Mice, Transgenic

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Humans

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Mice

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Medulloblastoma

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Cerebellar Neoplasms

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Receptors, Antigen, T-Cell, alpha-beta

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Adoptive Transfer

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Immunotherapy, Adoptive

dc.title

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

dc.type

Journal article

duke.contributor.orcid

Wildes, T|0000-0001-8313-9144

duke.contributor.orcid

Grant, G|0000-0002-2651-4603

duke.contributor.orcid

Kurtzberg, J|0000-0002-3370-0703

duke.contributor.orcid

McLendon, R|0000-0001-6682-4588

pubs.begin-page

eaav9879

pubs.issue

11

pubs.organisational-group

Duke

pubs.organisational-group

School of Medicine

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Faculty

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Clinical Science Departments

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Institutes and Centers

pubs.organisational-group

Pathology

pubs.organisational-group

Pediatrics

pubs.organisational-group

Duke Cancer Institute

pubs.organisational-group

Institutes and Provost's Academic Units

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Initiatives

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Neurosurgery

pubs.organisational-group

Duke Innovation & Entrepreneurship

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Pediatrics, Transplant and Cellular Therapy

pubs.publication-status

Published

pubs.volume

5

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