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In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function
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B7-H3-redirected chimeric antigen receptor T cells target glioblastoma and neurospheres

Dean Nehama1, Natalia Di Ianni2, Silvia Musio2

  • 1Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.

Ebiomedicine
|August 31, 2019
PubMed
Abstract

Insights

B7-H3 is highly expressed in glioblastoma (GBM) and targeting it with chimeric antigen receptor T (CAR-T) cells effectively controls tumor growth. This makes B7-H3 a promising new target for GBM treatment.

Area of Science:

  • Oncology
  • Immunotherapy
  • Cancer Biology

Background:

  • Glioblastoma (GBM) has a poor prognosis, necessitating novel therapeutic strategies.
  • Current chimeric antigen receptor T (CAR-T) cell therapies for GBM face challenges due to antigen heterogeneity and tumor escape.
  • The identification of new, effective targets for CAR-T cell therapy in GBM is crucial.

Purpose of the Study:

  • To investigate the potential of B7-H3 as a therapeutic target for GBM.
  • To evaluate the efficacy of B7-H3-redirected CAR-T cells against GBM.

Main Methods:

  • Compared B7-H3 mRNA expression in GBM using TCGA data.
  • Validated B7-H3 protein expression via immunohistochemistry in patient samples.
  • Assessed the antitumor activity of B7-H3 CAR-T cells in GBM cell lines, patient-derived neurospheres, and xenograft models.

Main Results:

  • B7-H3 is overexpressed in GBM tissues and patient-derived neurospheres, including those with cancer stem cells.
  • B7-H3-redirected CAR-T cells demonstrated effective control of GBM growth in vitro and in vivo.
  • Both CD28 and 4-1BB co-stimulation supported CAR-T cell activity, with CD28 showing higher cytokine release.

Conclusions:

  • B7-H3 is a highly expressed and promising target antigen for CAR-T cell therapy in GBM.
  • B7-H3-redirected CAR-T cells show significant potential for controlling GBM tumor growth.
  • Further development of B7-H3-targeted CAR-T cells could improve outcomes for GBM patients.
Keywords:
B7-H3Cancer stem cellsChimeric antigen receptorGlioblastomaImmunotherapy

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