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e-Poster Display Session

26P - Cellulose beads prepared in deep eutectic solvent function as carrier and cytoprotective encapsulation matrix for CAR-T cells in T-cell therapy against glioblastoma cells

Date

09 Dec 2020

Session

e-Poster Display Session

Presenters

Sauli Vuoti

Citation

Annals of Oncology (2020) 31 (suppl_7): S1425-S1427. 10.1016/annonc/annonc390

Authors

S. Vuoti1, M. Saari2, K. Narasimha2, K. Reinikainen2

Author affiliations

  • 1 University of Jyväskylä, Jyvaskyla/FI
  • 2 Chembrain LTD, Kauhava/FI
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Abstract 26P

Background

Malignant brain tumors, including glioblastoma, represent some of the most difficult to treat of solid tumors. Chimeric antigen receptor (CAR) T cells are a promising immunotherapeutic modality, which utilizes the tumor targeting specificity of any antibody or receptor ligand to redirect the cytolytic potency of T cells. The unique properties of the central nervous system limit T cell entry and risks of immune-based toxicities in highly sensitive environments. This is especially the case for CAR-T cells due to their lability during transfer, manipulation, and storage. Convection Enhanced Delivery (CED) is a technique used to infuse sensitive therapeutic agents directly into the intracranial area continuously under pressure with an improved turnover. Although CED successfully delivers small therapeutic agents, this technique has failed to effectively deliver cells largely due to cell sedimentation or destruction during delivery.

Methods

To overcome the described limitations, we developed a cellulose-based hydrogel matrix with the aid of deep eutectic solvents. The prepared cellulose beads were studied for improving the stability and efficacy of CAR-T cells when utilizing CED. CAR-T cells submitted to CED were counted and the efficiency of delivery was determined. In addition to delivery, the ability of the encapsulated CAR-T cells to migrate and induce cytotoxicity on U87MG-cells was evaluated, and their safety studied using preclinical animal models.

Results

We display that the cellulose beads provided better efficacy for CAR-T cell delivery in CED and protected the cells under serum-free conditions and heat for extended periods of time. The biological activity of the cells was not deteriorated and therapeutic efficacy on glioblastoma cell lines was maintained without signs of increased toxicity when the cells were released from the cellulose bead carriers.

Conclusions

The biodegradable cellulose beads were capable of retaining CAR-T cells in suspension and enhanced cell viability in clinically relevant settings, while maintaining biological activity for therapeutic efficacy towards glioblastoma cell lines.

Legal entity responsible for the study

Chembrain Ltd.

Funding

Chembrain LTD.

Disclosure

S. Vuoti: Full/Part-time employment, The work presented in this abstract was conducted before start of employment: Eli Lilly. M. Saari: Full/Part-time employment: Chembrain Ltd. K. Narasimha: Full/Part-time employment: Chembrain Ltd. K. Reinikainen: Full/Part-time employment: Chembrain Ltd.

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