Successful patient recruitment to a TCR T-cell therapy trial: bringing together multiple outputs from iMATCH to scale-up future ATMP clinical trial activity
Author: Jessica Ritchie
Advanced Therapy Medicinal Products (ATMPs) is an umbrella term for a branch of therapies which utilise cells, tissues or genes for medicinal use (European Medicines Agency (EMA) n.d.). The three broad categories of ATMPs include adoptive cell therapies, gene therapies and tissue engineered therapies (The European Parliament and the Council of the European Union (2007)). ATMP clinical trials are a growing area of medicine, within malignant and non-malignant disease indications. Clinically, they have the potential to offer significant benefit to patients with unmet clinical needs. This case study will focus specifically on a T-cell Receptor (TCR) therapy, which is a specific type of adoptive cell therapy used in the treatment of solid cancers.
Adoptive cell therapies are logistically very complex to deliver within the health service, namely because they are not comparable to ‘off-the-shelf’ drugs which are manufactured using conventional pharmaceutical methods (Elverum and Whitman 2020). Oncology-based TCR T-cell therapy clinical trial products are made using T-cells which are collected from the blood of a patient or extracted directly from tumour tissue. The collected T-cells are then transported to the trial company’s manufacturing facility where they are genetically modified to target a specific protein expressed by the cancer. This allows the modified T-cells to target and kill cancer cells. Before the T-cells are administered, the patients receive chemotherapy (called lymphodepletion) to prepare their body for the T-cell infusion and help the new modified T-cells work more effectively. Following chemotherapy, the modified T-cells are then given back to the patient intravenously. A specialist infrastructure was therefore needed to facilitate the co-ordination, delivery, and management of these therapies at The Christie Hospital.
With iMATCH support, a specialist research team was created at The Christie – the Advanced Immune and Cell Therapy (AICT) team. The team comprises various roles including research nurses, clinical trials co-ordinators and doctors who have extensive training in the field of ATMPs– from trial set-up, regulatory issues, clinical governance, ATMP patient recruitment, management, and subsequent follow-up. The GSK T-cell therapy trial was therefore set-up within the AICT team.
iMATCH funding also supported education and training through the role of a specialist ATMP practice facilitator in the AICT team, who was pivotal in delivering the clinical and theoretical nursing education and training needed for ATMPs (e.g. T-cell administration and toxicity monitoring). This programme of education and training has been cemented further through the iMATCH funded, bespoke, ATMP Master of Science degree programme at the University of Manchester. Three members of staff from the AICT team have now graduated from this highly specialist course.
On an operational level, iMATCH funding has increased on-site apheresis capacity through the purchase of an additional apheresis machine and partial funding of an additional apheresis nurse. On site cell storage has been increased within our stem cell lab through the purchase of an additional liquid nitrogen storage tank for ATMP products. These resources were utilised during the recruitment and management of our GSK T-cell therapy patient.
This was the first patient to be recruited to an adoptive cell therapy trial in the AICT team – a huge achievement for all involved (see Image 1). The patient featured in a press release: https://theattc.wpengine.com/news/the-christie-recruits-first-patient-to-t-cell-solid-tumour-trial. This raised awareness of cell therapy in the solid tumour field and the work of The Christie in this area. Recruitment to this clinical trial is ongoing and The Christie is amongst the top recruiting sites for this study globally.
The creation of the AICT research team has allowed ATMP clinical trials to be set up more efficiently given the specialist knowledge and skills of our team members, especially our senior clinical trials co-ordinator. Work is ongoing across Manchester through the Clinical Trials Accelerator (CTAT) group to improve institutional readiness across sites delivering clinical trial and standard of care ATMPs. This is being done through the streamlining and standardisation of set-up documents, costs templates and contract documents, with an overall aim of continuing to up-scale ATMP delivery within iMATCH, the ATTC network and beyond.
Image 1: The trial patient being treated on the ward on the day of their cell infusion. Pictured with Jessica Ritchie – AICT team Research Nurse.
The Christie has a growing portfolio of adoptive cell therapy clinical trials. Subsequently, the AICT team knowledge and experience continues to increase in line with growing trial activity. Interest from commercial sponsors to run ATMP studies in the AICT team is ongoing, given our specialist ATMP infrastructure.
Elverum, K., Whitman, M. (2020) Delivering cellular and gene therapies to patients: solutions for realizing the potential of the next generation of medicine. Gene Ther 27, 537–544. https://doi.org/10.1038/s41434-019-0074-7
European Medicines Agency (EMA) (n.d.) Advanced therapy medicinal products: overview, Available at: Advanced therapy medicinal products: Overview | European Medicines Agency (europa.eu) [accessed 26/01/2022]
The European Parliament and the Council of the European Union (2007) ‘Regulation (EC) No 1394/2007 on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004’, Official Journal of the European Union, L(324), pp. 121–137.