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

Edikan A. Ogunnaike(University of North Carolina at Chapel Hill), Alain Valdivia(University of North Carolina at Chapel Hill), Mostafa Yazdimamaghani(University of North Carolina at Chapel Hill), E. Cintora León(University of North Carolina at Chapel Hill), Seema Nandi(University of North Carolina at Chapel Hill), Hannah Hudson(University of North Carolina at Chapel Hill), Hongwei Du(University of North Carolina at Chapel Hill), Simon Khagi(University of North Carolina at Chapel Hill), Zhen Gu(University of California, Los Angeles), Barbara Savoldo(University of North Carolina at Chapel Hill), Frances S. Ligler(University of North Carolina at Chapel Hill), Shawn Hingtgen(University of North Carolina at Chapel Hill), Gianpietro Dotti(University of North Carolina at Chapel Hill)
Science Advances
October 8, 2021
Cited by 83Open Access
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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.


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