"Since their discovery in 2006, induced pluripotent stem cells (iPSC) have demonstrated their importance to disease modelling, drug discovery and regenerative medicine. Using genes/transcription factors associated with embryonic maintenance, 'adult' somatic cells are reprogrammed or induced to an embryonic-like state. This creates cells with the properties of self-renewal and pluripotent potential (meaning they can be used to create any cell type) whilst alleviating the ethical constraints often associated with embryonic derived material. In addition, iPSCs cells may be used for autologous therapies (using the patient's own cells) or, with careful selection of the donor, allow HLA matched, O negative cell banks for multiple recipients (allogeneic therapies which use cells from different donors that are compatible with the immune system of the patient receiving the stem cell therapy).
To date, most research in iPSCs has been conducted at an early pre-clinical stage; a major challenge is to make the protocols for generating iPSCs suitable for clinical use. Many of the existing protocols require an enormous amount of quality testing because the viruses/genes/transcription factors may integrate into the genome, causing undesirable changes and increasing the risk of tumours if they are not cleared from the cells. mRNA reprogramming avoids these safety concerns as mRNA does not integrate into the genome and remains within the cell for only a short period. However, suitable clinical-grade protocols have not yet been fully developed for the manufacturing processes.
This project proposes a novel strategy for the derivation of clinical iPSCs which have the properties associated with human embryonic stem cells whilst being derived from minimal blood from adults. By using a non-integrating mRNA reprogramming method, the risk of tumour formation usually associated with other methods is avoided.
To make the process economically attractive, manufacturing procedures will be standardised to allow an automated work flow from donor material, reprogramming, iPSC generation and cell-banking. This will allow quicker and safer generation of clinical grade iPSCs for both allogeneic and autologous therapies and provide scope for commercialisation and licensing of the generated cell lines to the biotechnology sector.
Bringing together the expertise of RoslinCT and REPROCELL will provide a step change in the production of clinical grade iPSCs and centre this know-how and manufacturing within the UK."
"The Northern Alliance Advanced Therapies Treatment Centre (NAATTC) is a group of NHS hospitals and services. NAATTC has a wide geographical reach across Scotland and the North of England and is responsible for the health care of 15 million NHS patients.
Advanced therapies are becoming increasingly available with a growing number of companies developing them both in the UK and worldwide. They are based on the administration of gene- and cell-based products in specialities such as haematology, autoimmunity, hepatology, cardiology and ophthalmology. They are thought to be more effective than existing treatments and provide treatments for diseases where currently no effective therapy exists. However most are still in clinical trials.
Advanced therapies present significant challenges to healthcare providers compared with existing treatments. Addressing these challenges in the NHS will require development and dissemination of new skills for nurses, doctors, hospital pharmacists, NHS managers, and commissioners such as NHS England and the clinical commissioning groups (CCGs). It will also require changes in the way treatment is delivered.
The changes required in the NHS can only be properly implemented through partnership with the companies that are developing and providing advanced therapies to the NHS. Manufacturers will need assistance with clinical trials to ensure optimal trial design, effective recruitment into clinical trials, and long term follow up of outcomes. The manufacturing and distributing processes are complex and it is critical that these systems are integrated effectively with those within the NHS.
The NAATTC already has considerable experience of delivering advanced therapies and clinical trials and will use this experience to work with manufacturers (and their supply chains) to significantly increase their capacity to deliver advanced therapies effectively, safely, and seamlessly to patients within the NHS. It will identify gaps in our existing provision and develop solutions to narrow and eliminate the gaps. It will share the best practice that it develops to other ATTCs and to other NHS organisations.
The outcomes will be to deliver these promising therapies to NHS patients and to make the NHS a global leader in their delivery, creating health and wealth for the UK."
ReNeuron is a biotechnology company that is experienced in developing cell therapy treatments for degenerative diseases such as stroke rehabilitation and diseases of the retina, such as retinitis pigmentosa (RP), for which there are no known treatments. In RP, the light detecting photoreceptor cells in the eye die gradually over a period of time, and the ultimate consequence to the patient is vision loss. Our own preclinical scientific research shows that it is possible to either protect these photoreceptor cells from dying and/or replace the lost photoreceptors by injecting similar cells, from donated eye tissue, that are grown in culture in the laboratory. ReNeuron is currently conducting Phase I/II clinical studies in RP. The hRPC cells may have efficacy in many different retinal degenerative diseases of the eye, therefore, ReNeuron has ambitions to extend the use of hRPC into multiple indications. For our cell treatment therapy to fully exploit the market potential in the long term, we need to be able to make cells on an industrial scale, and we, therefore, need to be able to characterise and select more eye tissue donations. We must always ensure the quality and comparability of the hRPC cells during these clinical trials and when we eventually supply the market. Therefore, in this project our intention is to make new banks of cell product from different donors, and, develop scientifically validated assays to demonstrate that the cells that are produced from each donor have the same biological properties as the first cell product, and that these properties are maintained during the cell expansion that is part of the manufacturing process. These assays are essential to develop as they will form the basis of Quality Control of the cell product for use in humans, just like with other medicines. We have formed a consortium that will bring together expertise in all of the relevant areas that are needed to make this project a success. The UK has a strong position in developing cell therapies and the current project will add to strengthening this position. Also, if the project is successful, we will set the standards for the manufacture of multi-donor cell based therapies into the future.