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Sci Adv. 2019 Nov 27;5(11):eaav9879. doi: 10.1126/sciadv.aav9879. eCollection 2019 Nov.

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

Author information

1
University of Florida Brain Tumor Immunotherapy Program, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Lillian S. Wells Department of Neurosurgery, McKnight Brain Institute, University of Florida, Gainesville, FL, USA.
2
U.S. Army, 1600 Spearhead Division Ave., Fort Knox, KY, USA.
3
Department of Neurosurgery, Stanford University Medical Center, Palo Alto, CA, USA.
4
Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
5
Department of Pathology, Duke University Medical Center, Durham, NC, USA.
6
Department of Pediatrics, University of Florida, Gainesville, FL, USA.

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.

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