Fibrin gel enhances the antitumor effects of chimeric antigen receptor T cells in glioblastoma

Edikan A Ogunnaike; Alain Valdivia; Mostafa Yazdimamaghani; Ernesto Leon; Seema Nandi; Hannah Hudson; Hongwei Du; Simon Khagi; Zhen Gu; Barbara Savoldo; Frances S Ligler; Shawn Hingtgen; Gianpietro Dotti

doi:10.1126/sciadv.abg5841

Fibrin gel enhances the antitumor effects of chimeric antigen receptor T cells in glioblastoma

Sci Adv. 2021 Oct 8;7(41):eabg5841. doi: 10.1126/sciadv.abg5841. Epub 2021 Oct 6.

Authors

Edikan A Ogunnaike^{1

2

3}, Alain Valdivia⁴, Mostafa Yazdimamaghani^{1

3}, Ernesto Leon¹, Seema Nandi², Hannah Hudson¹, Hongwei Du¹, Simon Khagi^{1

5}, Zhen Gu^{6

7}, Barbara Savoldo^{1

8}, Frances S Ligler^{2

3}, Shawn Hingtgen⁴, Gianpietro Dotti^{1

9}

Affiliations

¹ Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
² Joint Department of Biomedical Engineering, North Carolina State University and University of North Carolina at Chapel Hill, Raleigh, NC 27695, USA.
³ Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
⁴ Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁵ Department of Medicine, Division of Medical Oncology, University of North Carolina, Chapel Hill, NC 27599, USA.
⁶ Department of Bioengineering, University of California, Los Angeles, CA 90095, USA.
⁷ College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.
⁸ Department of Pediatrics, University of North Carolina, Chapel Hill, NC 27514, USA.
⁹ Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599, USA.

Abstract

Regional delivery of chimeric antigen receptor (CAR) T cells in glioblastoma represents a rational therapeutic approach as an alternative to intravenous administration to avoid the blood-brain barrier impediment. Here, we developed a fibrin gel that accommodates CAR-T cell loading and promotes their gradual release. Using a model of subtotal glioblastoma resection, we demonstrated that the fibrin-based gel delivery of CAR-T cells within the surgical cavity enables superior antitumor activity compared to CAR-T cells directly inoculated into the tumor resection cavity.

Abstract

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