Many forms of cancer fail multiple treatments which leaves patients with advanced cancer which has spread and is incurable. However, one of the most promising avenues to treat this type of cancer is Adoptive Cell Therapy, especially Chimeric Antigen T Cell Therapy (CAR-T) which genetically modifies a patients own T cells, outside the body, grows them to huge numbers then adds them back to the patient to target and fight cancer. Already, this has shown much promise in treating diseases such as childhood leukaemia. However, targeting solid tumours such as lung or colon cancers, which account for around 74,000 deaths annually in the UK alone, is more challenging.
On TRACK
Dr David Coe, from the University of Bristol’s School of Cellular and Molecular Medicine, received a grant from the Elizabeth Blackwell Institute TRACK Awards (Translational Acceleration and Knowledge Transfer) to develop and test the suitability of novel methods to target these cells to solid tumours more effectively.
“Applying Adoptive Cell Therapy to solid tumours, particularly in older patients, is challenging,” said Dr Coe. “Part of that challenge is purifying immune cells that successfully migrate to solid tumours. Clinical trials with CAR-T therapies that have been successful in treating liquid tumours have mixed efficacy treating solid tumours partly due to low migration of T cells to the tumour”.
The Column of Expansion and Differentiation Bioreactor (CoED) that Dr Coe was trialling in this project aims to create highly purified Tc cells that are imprinted with the ability to migrate to the tumour site and attack the tumour.
What is CoED?
The Column of Expansion and Differentiation Bioreactor utilises the capacity of T cells to move around the body to purify, activate and manipulate them. In this way, the system can create T cells targeted towards a specific tumour or tissue. The CoED Bioreactor is made of stackable individual chambers horizontally separated from each other with a layer of plastic which is perforated by microscopic pores. As the cells migrate through the pores to the different chambers, they are activated by a variety of different proteins tailored to the cancer requiring treatment. From completely naïve cells at the start, the cells collected from the final chamber are tailored to migrate to specific organs or tumours, without costly and complicated genetic manipulation.
Pilot study
“Thanks to funding from the Elizabeth Blackwell Institute,” said Dr Coe, “we can demonstrate for the first time that the CoED Bioreactor can purify and differentiate an enriched population of effector T cells from human blood samples. These results pave the way for further developments to test the increased potency, tumour specific migration and expansion of CoED derived T cells on a larger scale for different treatment applications.”
The Institute’s TRACK awards, which focus on projects with potentially commercial applications, have been key in founding numerous commercial enterprises for University of Bristol researchers who wish to branch out into industry.
“Having demonstrated a successful purification,” said Dr Coe, “we can now test the CoED system with tumour targeted immune cells to demonstrate whether we can improve the ability of tumour targeting cells to migrate to and kill tumours. This system has the potential to create better, more targeted treatments for a variety of cancers at stages previously thought to be challenging to treat.”
Development after the TRACK Award
Dr Coe said “Winning the TRACK award significantly boosted my confidence in the CoED Bioreactor technology which meant I had the belief in the technology and myself to gain a place on the Science Creates Accelerator Programme in September 2023. As part of this entrepreneurial programme, CoED Biosciences Ltd was formed on the 12th of September 2023 and we filed a patent application for the CoED Bioreactor on the 18th March 2024.”
CoED Biosciences has just presented their technology for the first time in the startup zone of the Advanced Therapies Conference where there was a lot of interest from cell therapy companies.
Figure 1. The CoED Bioreactor purifies cells based on their ability to migrate through a cell permeable membrane in response to a specified set of chemokines. Naive cells migrate from tissues in Niche 1 to Niche 2. In Niche 2 cells are activated so that they change their migratory phenotype. Activated cells are then recruited to Niche 3 by a set of chemokines specific for activated cells. Purified, differentiated, proliferating cells are harvested from Niche 3. This system mimics the natural migration of immune cells in and out of lymph nodes.