Publications by authors named "Jason K Yokoyama"

Article Synopsis
  • The study focuses on a novel treatment for diffuse intrinsic pontine glioma (DIPG), a deadly brainstem tumor, using B7-H3-targeted chimeric antigen receptor (CAR) T cells.
  • A phase I trial (BrainChild-03) was conducted with three DIPG patients, where they received 40 infusions of B7-H3 CAR T cells, showing no severe toxic effects.
  • Results indicated one patient experienced significant improvement, and there was evidence of local immune activation and persistent CAR T cells in the patients' cerebrospinal fluid (CSF), suggesting this treatment approach's potential effectiveness.
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Locoregional delivery of chimeric antigen receptor (CAR) T cells has resulted in objective responses in adults with glioblastoma, but the feasibility and tolerability of this approach is yet to be evaluated for pediatric central nervous system (CNS) tumors. Here we show that engineering of a medium-length CAR spacer enhances the therapeutic efficacy of human erb-b2 receptor tyrosine kinase 2 (HER2)-specific CAR T cells in an orthotopic xenograft medulloblastoma model. We translated these findings into BrainChild-01 ( NCT03500991 ), an ongoing phase 1 clinical trial at Seattle Children's evaluating repetitive locoregional dosing of these HER2-specific CAR T cells to children and young adults with recurrent/refractory CNS tumors, including diffuse midline glioma.

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Background: Though currently approved immunotherapies, including chimeric antigen receptor T cells and checkpoint blockade antibodies, have been successfully used to treat hematological and some solid tumor cancers, many solid tumors remain resistant to these modes of treatment. In solid tumors, the development of effective antitumor immune responses is hampered by restricted immune cell infiltration and an immunosuppressive tumor microenvironment (TME). An immunotherapy that infiltrates and persists in the solid TME, while providing local, stable levels of therapeutic to activate or reinvigorate antitumor immunity could overcome these challenges faced by current immunotherapies.

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