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Updated: Jun 15, 2026
A Syngeneic Mouse B-Cell Lymphoma Model for Pre-Clinical Evaluation of CD19 CAR T Cells
Published on: October 16, 2018
Comparative evaluation of CAR-expressing T-, NK-, NKT-cells, and macrophages in an immunocompetent mouse glioma model
Ryusuke Hatae1, Payal B Watchmaker1, Akane Yamamichi1
1Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Background:
While chimeric antigen receptor (CAR) T-cells are promising, there is a rapidly growing interest in developing other CAR-expressing immune cells. However, to date, no reported studies evaluated these cells side-by-side in immune-competent glioma models.
Methods:
We developed a novel C57BL/6-background transgenic mouse strain with all hematopoietic cells carrying the anti-epidermal growth factor receptor (EGFR)vIII-CAR downstream of a Lox-Stop-Lox cassette in the Rosa26 locus. Crossing with mice transgenic for Vav-Cre allowed the expression of anti-EGFRvIII CAR in all hematopoietic cells. In particular, we evaluated CAR-T, CAR-NKT, CAR-NK-cells, and CAR-macrophages in a syngeneic mouse SB28EGFRVIII glioma model.
Results:
CAR-NK and CAR-NKT-cells demonstrated anti-tumor effects comparable to CAR-T cells in vitro. A single intratumoral administration of CAR-T and CAR-NKT cells in combination mediated superior therapeutic efficacy compared to CAR-T cells or CAR-NKT-cells alone. A single intravenous infusion of CAR-NK cells following lymphodepletion failed to mediate significant anti-glioma effects. Additionally, intratumoral injection of CAR-NK cells did not confer therapeutic benefit. Contrary to previous reports using human macrophages, CAR-macrophages did not demonstrate enhanced antigen-presentation activity against glioma cells compared to non-CAR macrophages. Intratumorally administered CAR-macrophages failed to demonstrate local persistence or anti-tumor effects in vivo.
Conclusions:
These data provide a valuable basis as to which immune cells can mediate effective anti-glioma response in an immuno-competent glioma environment. Our data also suggest that a combination of CAR-T and CAR-NKT-cells may represent a promising therapeutic strategy.
Insights
Chimeric antigen receptor (CAR) T-cells and CAR-NKT-cells show promise against glioma. Combining CAR-T and CAR-NKT-cells demonstrated superior therapeutic efficacy in immune-competent models.
Area of Science:
- Immunotherapy
- Oncology
- Cellular Therapy
Background:
- Chimeric antigen receptor (CAR) T-cells are a promising cancer therapy.
- Interest is growing in other CAR-expressing immune cells for cancer treatment.
- No studies have directly compared different CAR-immune cells in immune-competent glioma models.
Purpose of the Study:
- To evaluate and compare CAR-T, CAR-NKT, CAR-NK cells, and CAR-macrophages in an immune-competent glioma model.
- To assess the therapeutic efficacy of these CAR-modified immune cells against glioma.
- To identify optimal CAR-immune cell strategies for glioma treatment.
Main Methods:
- Developed a novel transgenic mouse model expressing anti-EGFRvIII CAR in all hematopoietic cells.
- Evaluated CAR-T, CAR-NKT, CAR-NK cells, and CAR-macrophages in a syngeneic mouse glioma model.
- Administered CAR-immune cells via intratumoral injection or intravenous infusion.
Main Results:
- CAR-NK and CAR-NKT cells showed comparable in vitro anti-tumor effects to CAR-T cells.
- Combined CAR-T and CAR-NKT cell administration yielded superior therapeutic efficacy.
- CAR-NK cells and CAR-macrophages failed to demonstrate significant anti-glioma effects in vivo.
- CAR-macrophages did not show enhanced antigen presentation compared to non-CAR macrophages.
Conclusions:
- CAR-T and CAR-NKT cells are effective against glioma in immune-competent models.
- Combination therapy with CAR-T and CAR-NKT cells shows significant therapeutic potential.
- This study provides a basis for selecting immune cells for anti-glioma immunotherapy.
