Public Funding for The Automation Partnership (Cambridge) Limited

To design and develop novel bioprocesses and vessels for optimal therapeutic protein and cell therapy production using the automated ambr250 bioreactor platform.

The project aim is for TAP Biosystems, The Cell Therapy Catapult and University College London to develop a small scale benchtop bioreactor that can be applied to cell therapy appliations, to test and validate the performance of the new bioreactor system with exemplar cell line expansion processes representative of both allogeneic and autologous therapies, and to gather input from regultory agencies on the appropriate levels of validation required for the system to be adopted into GMP facilities. An extensive commerical and market research activity will ensure the biorector has the appropriate user requirement specifications for both allogenic and autologous cell therapy applications that can advance the development and commercialisation of cell therapies by providing a tool for scaled down process optimisation and small scale production are affordable, well characterised and scaleable. Achieving this will reduce cell therapy development cost and time and acclerate delivery novel cell therapies to patients.

We plan to develop a novel ‘living nerve growth guide’ as an off the shelf therapy to treat peripheral nerve injury, which can cause lifelong pain and disability and is a significant unmet medical need. Our therapy would substitute for an autograft, the current ‘gold standard’ for peripheral nerve repair. Partners TAP Biosystems and The Open University have already shown that combining their novel tissue engineering technologies enables robust, self-aligning cellular tissues to be made from collagen. These mimic the structure of peripheral nerve and support neuronal regeneration in vivo. In this project we will build on initial work using partner ReNeuron’s clinical grade neural stem cells. We will develop production tools, optimise the process, characterise the properties of our living nerve growth guide and then carry out efficacy tests of nerve regeneration. Success in the project will provide initial proof of concept data, so that this novel therapy can progress towards the clinic.

We plan to develop a novel, automated cell culture system specifically designed for iPSC and autologous cell culture. Early stage iPS cell culture is very labour intensive since cells must be monitored and fed daily for many weeks. For clinical applications cells must be cultured in a GMP clean room environment, with high staff and infrastructure costs. Our system will automate routine feeding, monitoring and incubation of cells in a 'closed', low cost unit, with remote monitoring and operation. It will maintain multiple plates of cells from one patient, to ensure segregation, within a small footprint, and be GMP compliant. We aim to deliver more consistent, higher quality cells, to minimise the cost, resource and 'hands on' time needed for iPSC and autologous cell culture, and to address a major barrier to wider adoption of iPSC for pre-clinical and clinical studies. The partners, TAP Biosystems, The Wellcome Trust Sanger Institute and University of Cambridge together have outstanding track records in developing innovative automation for cell culture and world class stem cell research, with a broad focus on developing and translating iPSC-based research into novel therapies.

TAP Biosystems and UCL Institute of Ophthalmology are developing a novel, patented technology (RAFT) that enables 3D tissue equivalents to be manufactured from collagen simply and reproducibly. The RAFT process creates tissue-like architectures that we are using to develop a corneal therapy - with embossed surface topography to replicate the in vivo stem cell niche - to support ocular surface regeneration. Results are very promising; we can reproducibly make multilayered ocular epithelia with morphology and protein markers very like the normal human cornea. We have advanced preclinical work, defining safety testing, regulatory pathway and the basis for QC assays. Our aim in this project is to complete preclinical testing, obtain regulatory and ethical approval, then manufacture the therapy in GMP conditions and perform a small first in man safety study at Moorfields Eye Hospital under Specials Hospitals Exemption arrangements. The data from this study would enable us to progress towards phase I/II clinical trials.

Awaiting Public Summary

The aim is to develop a process which can distinguish good from bad induced pluripotent stem cells (iPS cells) in terms of their differentiation capacity. Batches of iPS cells derived from multiple patient tissue samples will be analysed and grouped in terms of their ability to differentiate into the three cell lineages (endoderm, mesoderm and ectoderm). The key epigenetic marks which are the most important as distinguishing features to be able to divide them into “good” (those which can fully differentiate) versus “bad” (those which can’t) cell lines will be determined. Thus, the output of the project will be an optimised and validated key signature gene set predictive of the iPS cells differentiation capacity which would form the basis of a diagnostic tool

TAP Biosystems and UCL Institute of Ophthalmology are developing a novel, patented technology (RAFT) that enables 3D tissue equivalents to be manufactured from collagen simply and reproducibly. The RAFT process creates a tissue-like architecture that we are using to develop a corneal therapy - with embossed surface topology to replicate the in vivo stem cell niche - to support ocular surface regeneration. Results are very promising; we can reproducibly make multilayered ocular epithelia with morphology and protein markers very like the normal human cornea. We have advanced preclinical work, defining safety testing, regulatory pathway and the basis for QC assays. Our aim in this project is to complete preclinical testing, obtain regulatory and ethical approval, then manufacture the therapy in GMP conditions and perform a small first in man safety study at Moorfields Eye Hospital under Specials Hospitals Exemption arrangements. The data from this study would enable us to progress towards phase I/II clinical trials.

Awaiting Public Summary

The project seeks to design and build a flexible robotic platform to automate incubation and processing of hundreds of mammalian cell cultures growing in shake flasks, with integrated cell growth and metabolite analysis. Shake flasks model larger scale bioreactors, have ample volume for frequent sampling for analysis and support process development and cell line stability studies. The goal is to ensure consistent, reproducible cell processing for high throughput bioprocess research. This would facilitate systematic, parallel investigation of multiple parameters influencing cell growth or productivity, e.g. media formulation or feed regime. "Smart" software would be developed to model the process and mimic the culture expert, and thus automatically decide how and when to process each individual culture e.g. subculture to a target cell count, or when to feed to maintain a set glucose level.