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IL7 and IL7 Flt3L co-expressing CAR T cells improve therapeutic efficacy in mouse EGFRvIII heterogeneous glioblastoma.

Publication ,  Journal Article
Swan, SL; Mehta, N; Ilich, E; Shen, SH; Wilkinson, DS; Anderson, AR; Segura, T; Sanchez-Perez, L; Sampson, JH; Bellamkonda, RV
Published in: Front Immunol
2023

Chimeric antigen receptor (CAR) T cell therapy in glioblastoma faces many challenges including insufficient CAR T cell abundance and antigen-negative tumor cells evading targeting. Unfortunately, preclinical studies evaluating CAR T cells in glioblastoma focus on tumor models that express a single antigen, use immunocompromised animals, and/or pre-treat with lymphodepleting agents. While lymphodepletion enhances CAR T cell efficacy, it diminishes the endogenous immune system that has the potential for tumor eradication. Here, we engineered CAR T cells to express IL7 and/or Flt3L in 50% EGFRvIII-positive and -negative orthotopic tumors pre-conditioned with non-lymphodepleting irradiation. IL7 and IL7 Flt3L CAR T cells increased intratumoral CAR T cell abundance seven days after treatment. IL7 co-expression with Flt3L modestly increased conventional dendritic cells as well as the CD103+XCR1+ population known to have migratory and antigen cross-presenting capabilities. Treatment with IL7 or IL7 Flt3L CAR T cells improved overall survival to 67% and 50%, respectively, compared to 9% survival with conventional or Flt3L CAR T cells. We concluded that CAR T cells modified to express IL7 enhanced CAR T cell abundance and improved overall survival in EGFRvIII heterogeneous tumors pre-conditioned with non-lymphodepleting irradiation. Potentially IL7 or IL7 Flt3L CAR T cells can provide new opportunities to combine CAR T cells with other immunotherapies for the treatment of glioblastoma.

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Published In

Front Immunol

DOI

EISSN

1664-3224

Publication Date

2023

Volume

14

Start / End Page

1085547

Location

Switzerland

Related Subject Headings

  • T-Lymphocytes
  • Mice
  • Interleukin-7
  • Glioma
  • Glioblastoma
  • ErbB Receptors
  • Animals
  • 3204 Immunology
  • 3105 Genetics
  • 3101 Biochemistry and cell biology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Swan, S. L., Mehta, N., Ilich, E., Shen, S. H., Wilkinson, D. S., Anderson, A. R., … Bellamkonda, R. V. (2023). IL7 and IL7 Flt3L co-expressing CAR T cells improve therapeutic efficacy in mouse EGFRvIII heterogeneous glioblastoma. Front Immunol, 14, 1085547. https://doi.org/10.3389/fimmu.2023.1085547
Swan, Sheridan L., Nalini Mehta, Ekaterina Ilich, Steven H. Shen, Daniel S. Wilkinson, Alexa R. Anderson, Tatiana Segura, Luis Sanchez-Perez, John H. Sampson, and Ravi V. Bellamkonda. “IL7 and IL7 Flt3L co-expressing CAR T cells improve therapeutic efficacy in mouse EGFRvIII heterogeneous glioblastoma.Front Immunol 14 (2023): 1085547. https://doi.org/10.3389/fimmu.2023.1085547.
Swan SL, Mehta N, Ilich E, Shen SH, Wilkinson DS, Anderson AR, et al. IL7 and IL7 Flt3L co-expressing CAR T cells improve therapeutic efficacy in mouse EGFRvIII heterogeneous glioblastoma. Front Immunol. 2023;14:1085547.
Swan, Sheridan L., et al. “IL7 and IL7 Flt3L co-expressing CAR T cells improve therapeutic efficacy in mouse EGFRvIII heterogeneous glioblastoma.Front Immunol, vol. 14, 2023, p. 1085547. Pubmed, doi:10.3389/fimmu.2023.1085547.
Swan SL, Mehta N, Ilich E, Shen SH, Wilkinson DS, Anderson AR, Segura T, Sanchez-Perez L, Sampson JH, Bellamkonda RV. IL7 and IL7 Flt3L co-expressing CAR T cells improve therapeutic efficacy in mouse EGFRvIII heterogeneous glioblastoma. Front Immunol. 2023;14:1085547.

Published In

Front Immunol

DOI

EISSN

1664-3224

Publication Date

2023

Volume

14

Start / End Page

1085547

Location

Switzerland

Related Subject Headings

  • T-Lymphocytes
  • Mice
  • Interleukin-7
  • Glioma
  • Glioblastoma
  • ErbB Receptors
  • Animals
  • 3204 Immunology
  • 3105 Genetics
  • 3101 Biochemistry and cell biology