Journal
SCIENCE ADVANCES
Volume 5, Issue 11, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.aav9879
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Funding
- National Cancer Institute [R01 CA195563]
- V Foundation for Cancer Research Translational Research Award
- Hyundai Hope On Wheels Quantum Award
- American Brain Tumor Association Research Collaboration Grant
- Alex's Lemonade Stand Young Investigator Grant
- Florida Center for Brain Tumor Research Grant
- University of Florida Health Cancer Center Predoctoral Award
- Wells Foundation
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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 V. 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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