American Association for Cancer Research
Browse
- No file added yet -

Supplementary Data from Intraventricular B7-H3 CAR T Cells for Diffuse Intrinsic Pontine Glioma: Preliminary First-in-Human Bioactivity and Safety

Download (14.97 MB)
journal contribution
posted on 2023-04-04, 00:20 authored by Nicholas A. Vitanza, Ashley L. Wilson, Wenjun Huang, Kristy Seidel, Christopher Brown, Joshua A. Gustafson, Jason K. Yokoyama, Adam J. Johnson, Blake A. Baxter, Ryan W. Koning, Aquene N. Reid, Michael Meechan, Matthew C. Biery, Carrie Myers, Stephanie D. Rawlings-Rhea, Catherine M. Albert, Samuel R. Browd, Jason S. Hauptman, Amy Lee, Jeffrey G. Ojemann, Michael E. Berens, Matthew D. Dun, Jessica B. Foster, Erin E. Crotty, Sarah E.S. Leary, Bonnie L. Cole, Francisco A. Perez, Jason N. Wright, Rimas J. Orentas, Tony Chour, Evan W. Newell, Jeffrey R. Whiteaker, Lei Zhao, Amanda G. Paulovich, Navin Pinto, Juliane Gust, Rebecca A. Gardner, Michael C. Jensen, Julie R. Park
Supplementary Data from Intraventricular B7-H3 CAR T Cells for Diffuse Intrinsic Pontine Glioma: Preliminary First-in-Human Bioactivity and Safety

Funding

Cookies for Kid’s Cancer

DIPG All-In

Matthew Larson Foundation

NCI Clinical Proteomics Tumor Analysis Consortium

NCI Academic Industrial Partnership

NCI Research Specialist Program

Alex's Lemonade Stand Foundation for Childhood Cancer (ALSF)

Cancer Moonshot (Misión contra el Cáncer)

National Center for Advancing Translational Sciences (NCATS)

United States Department of Health and Human Services

Find out more...

St. Baldrick’s Foundation (SBF)

History

ARTICLE ABSTRACT

Diffuse intrinsic pontine glioma (DIPG) remains a fatal brainstem tumor demanding innovative therapies. As B7-H3 (CD276) is expressed on central nervous system (CNS) tumors, we designed B7-H3–specific chimeric antigen receptor (CAR) T cells, confirmed their preclinical efficacy, and opened BrainChild-03 (NCT04185038), a first-in-human phase I trial administering repeated locoregional B7-H3 CAR T cells to children with recurrent/refractory CNS tumors and DIPG. Here, we report the results of the first three evaluable patients with DIPG (including two who enrolled after progression), who received 40 infusions with no dose-limiting toxicities. One patient had sustained clinical and radiographic improvement through 12 months on study. Patients exhibited correlative evidence of local immune activation and persistent cerebrospinal fluid (CSF) B7-H3 CAR T cells. Targeted mass spectrometry of CSF biospecimens revealed modulation of B7-H3 and critical immune analytes (CD14, CD163, CSF-1, CXCL13, and VCAM-1). Our data suggest the feasibility of repeated intracranial B7-H3 CAR T-cell dosing and that intracranial delivery may induce local immune activation. This is the first report of repeatedly dosed intracranial B7-H3 CAR T cells for patients with DIPG and includes preliminary tolerability, the detection of CAR T cells in the CSF, CSF cytokine elevations supporting locoregional immune activation, and the feasibility of serial mass spectrometry from both serum and CSF.This article is highlighted in the In This Issue feature, p. 1

Usage metrics

    Cancer Discovery

    Categories

    Keywords

    cancer

    Licence

    CC BY

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC