Improving patient care though the optimisation of cell therapy cryopreservation and CAR-T manufacturing capacity

Research question What are the optimal conditions for shipping, cryopreserving and manufacturing cell therapies used to treat patients. Background There are approximately 5,000 Blood and Marrow Transplants (BMT) in England every year.

Changes in clinical practice, largely due to the Covid pandemic, have led to increased rates of cryopreservation of allogeneic donations prior to transplant in addition to the ongoing cryopreservation of autologous HPC collections.

Additionally, the advent of CAR-T and related immune therapies has resulted in a rapidly growing need to cryopreserve apheresis products destined for genetic modification.

However, several studies have suggested that cryopreservation can lead to delayed engraftment and inferior patient outcomes. Aims and Objectives Our aim is to optimise the quality and economic delivery of both existing and new cell therapies.

We will achieve this by: - improving collection capacity and cell processing yields, thereby increasing UK capacity for CAR-T manufacturing as a point of care treatment - enhancing product viability during transit and cryopreservation, thereby reducing overall costs to the NHS whilst increasing patient safety. - improving quality control through the development of more targeted cell therapy assays, enabling a better link between cell phenotype, dose, cryopreservation and engraftment times, thus reducing risks to immunocompromised patients and the cost of hospital stays.

Methods - Validate more targeted Quality control (QC) protocols to assay the potency of specific subsets of HPC and immune cells to enable a better link between cell dose pre- and post-cryopreservation and patient outcomes. - Validate cell product storage temperature, times and cryopreservative solutions with reduced DMSO or alternative cryoprotectants. - Develop end-to-end closed processing workflows to improve product safety and minimise infrastructure and processing costs for HPC and CAR-T products.

Timelines for delivery Initial work will focus on the development of improved and validated QC assays to support subsequent work on optimising cryopreservation.

With the new assays and test materials already available to NHSBT the work will move on to optimising cell selection, storage and cryopreservation protocols using alternatives to DMSO for the latter.

The processing changes will include moving to closed processing alongside improvements to CAR-T manufacturing and efficacy protocols.

Anticipated Impact and Dissemination Improvements made during this project will be made available to the network of 6 HTA licensed and JACIE accredited laboratories that NHSBT manages in support BMT activity in England.

NHSBT also works with academic and commercial organisations to develop, manufacture and distribute a range of new cell and gene therapies under MHRA license as part of clinical trials and the improvements will be applied here too.

The protocols developed under this funding will be rolled out to the multiple sites supporting BMT and those offering point of care manufacturing for large numbers of patients.

Successful outputs from the project will be published in the scientific literature and made available through presentation at national and international forums for others to also adopt. Information and feedback will be made available to patients via the PPIE lead and an annual review meeting.