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Investigating the Optimal Storage Conditions for the Manufacture and Delivery of CAR-T cells

Alhubaysh, Abeer Abdullah; (2023) Investigating the Optimal Storage Conditions for the Manufacture and Delivery of CAR-T cells. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Adaptive cellular therapies, including the more recently approved CAR-T cells, are highly dependent on the delivery of cryopreserved material. However, several strategies of delivery are restricted as a result of the complications associated with the transfer of liquid nitrogen (LN2) and the influence of toxic agents found in most cryoprotectants resulting in the loss of cell number and function within the final product. This doctoral thesis aims to investigate alternative solutions to the preservation of CAR-T cells for the efficient transfer between lab to clinic without the need for toxic cryoprotectants or sub-zero temperatures. This was achieved by exploring hypothermic storage solutions as an alternative to cryopreservation of T and CART cells. Furthermore, the influence of encapsulating CAR-T cells in serum-free media was also assessed for prolong the storage of cells. CAR-T cells stored at ambient temperature using XVIVOTM 15 serum-free media achieved comparable results to cells cryopreserved in -80 ºC and LN2 (-196 ºC) with regards to cell viability (%) and cytotoxic functions within 7 days of storage, thus eliminating the need for toxic cryoprotectant agents. The encapsulation of CAR-T cells sealed for extended storage at 24 ºC without gas exchange showed a 60% of lysis target cells (Nalm-6) following 2 weeks of storage when co-incubated for 24 hours, in comparison to nonencapsulated CAR-T cells. This research therefore presents a suitable alternative for the storage of CAR-T cells with scope for applying this to other cell therapies. In addition, it will support both point-of-care and decentralized manufacturing.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Investigating the Optimal Storage Conditions for the Manufacture and Delivery of CAR-T cells
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10163045
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