<i>In vitro</i> encapsulation and expansion of T and CAR-T cells using 3D synthetic thermo-responsive matrices

Lizana-Vasquez, Gaby D.; Mendez-Vega, Janet; Cappabianca, Dan; Saha, Krishanu; Torres-Lugo, Madeline

doi:10.1039/d4ra01968g

RSC Adv.

2024

DOI: 10.1039/d4ra01968g

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In vitro encapsulation and expansion of T and CAR-T cells using 3D synthetic thermo-responsive matrices

Gaby D. Lizana-Vasquez,

Janet Mendez-Vega,

Dan Cappabianca

et al.

Abstract: This work employed a biocompatible and synthetic-based thermo-responsive material with tailored mechanical properties as a potential macro-scale scaffold to support ex vivo T and CAR-T cell encapsulation and culture.

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In Vitro Assessment of Thermo‐Responsive Scaffold as a 3D Synthetic Matrix for CAR‐T Potency Testing Against Glioblastoma Spheroids

Lizana‐Vasquez,

Ramasubramanian,

Davarzani

et al. 2024

J Biomedical Materials Res

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Chimeric antigen receptor (CAR) T cell immunotherapy has demonstrated exceptional efficacy against hematological malignancies, but notably less against solid tumors. To overcome this limitation, it is critical to investigate antitumor CAR‐T cell potency in synthetic 3D microenvironments that can simulate the physical barriers presented by solid tumors. The overall goal of this study was the preliminary assessment of a synthetic thermo‐responsive material as a substrate for in vitro co‐cultures of anti‐disialoganglioside (GD2) CAR‐T cells and patient‐derived glioblastoma (GBM) spheroids. Independent co‐culture experiments demonstrated that the encapsulation process did not adversely affect the cell cycle progression of glioma stem cells (GSCs) or CAR‐T cells. GSC spheroids grew over time within the terpolymer scaffold, when seeded in the same ratio as the suspension control. Co‐cultures of CAR‐T cells in suspension with hydrogel‐encapsulated GSC spheroids demonstrated that CAR‐T cells could migrate through the hydrogel and target the encapsulated GSC spheroids. CAR‐T cells killed approximately 80% of encapsulated GSCs, while maintaining effective CD4:CD8 T cell ratios and secreting inflammatory cytokines after interacting with GD2‐expressing GSCs. Importantly, the scaffolds also facilitated cell harvesting for downstream cellular analysis. This study demonstrated that a synthetic 3D terpolymer hydrogel can serve as an artificial scaffold to investigate cellular immunotherapeutic potency against solid tumors.

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In Vitro Assessment of Thermo‐Responsive Scaffold as a 3D Synthetic Matrix for CAR‐T Potency Testing Against Glioblastoma Spheroids

Lizana‐Vasquez,

Ramasubramanian,

Davarzani

et al. 2024

J Biomedical Materials Res

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show abstract

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In vitro encapsulation and expansion of T and CAR-T cells using 3D synthetic thermo-responsive matrices

Abstract: This work employed a biocompatible and synthetic-based thermo-responsive material with tailored mechanical properties as a potential macro-scale scaffold to support ex vivo T and CAR-T cell encapsulation and culture.

Cited by 1 publication

References 79 publications

In Vitro Assessment of Thermo‐Responsive Scaffold as a 3D Synthetic Matrix for CAR‐T Potency Testing Against Glioblastoma Spheroids

In Vitro Assessment of Thermo‐Responsive Scaffold as a 3D Synthetic Matrix for CAR‐T Potency Testing Against Glioblastoma Spheroids

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