Precision cell therapies represent an opportunity for transformational change in solid tumour cancer treatment. Whilst novel modalities are supported by increasingly innovative manufacturing platforms, challenges surrounding process closure and reproducibility remain at the industry’s core. A dearth of fully closed systems to support tumour infiltrating lymphocyte (TIL) product manufacture has catalysed Achilles Therapeutics to develop a bespoke technology to address these shortcomings, with the challenges and learnings discussed herein.

IMA203 & IMA203CD8 are Immatics’ TCR T product candidate(s) using a PRAME-specific TCR with or without a CD8 co-receptor. Manufacturing improvements implemented enhance key features of the cell product. Continuous enhancements are in progress in preparation of later-stage clinical trials.

There are longstanding challenges in the commercialisation of ATMPs that can be addressed by the implementation of process analytical technologies (PATs). Cell and Gene Therapy Catapult (CGTC) has led a consortium project with 23 collaborators to investigate the application of PAT and advanced analytics for a T-Cell immunotherapy process. We will describe results from the online, in-line and at-line PATs employed in the study discussing the different applications and implementations.

Gene and cell therapies are gaining more and more interest in personalized precision medicine. From a manufacturing perspective, cell therapies are fairly demanding, requiring chemical gene synthesis, plasmid DNA fermentation and purification, along with viral vector design and production via mammalian cell cultures, isolation of human T cells from the patient or allogenic T cells, propagation of the T cells and transfection with the viral vector carrying the gene of interest for a ligand on the T cell surface targeting the T cell to the tumor cell to express their cytotoxic effect. Or coupling monoclonal antibodies to the surface of the T cell to target the tumor cell. An end-to-end supplier for all required manufacturing technologies is advisable and will facilitate the process chain.

Ongoing NK cell clinical trials suggest a therapeutic role for NK cells in various types of cancer. Impaired/dysfunctional immune cells in cancer patients highlight the need for an external supply of highly potent NK cells to repopulate the immune system. A scalable NK cell product, which is off the shelf and can be cryopreserved is the key to meet the unmet needs and for a successful commercialisation”. We will provide an overview of Glycostem’s allogeneic NK cell product oNKord® progress on the road to commercialisation.

Organoid-based implant manufacturing may enable the production of complex 3D ATMP implants able to revolutionise defect regeneration and restore organ function. Engineering such complex ATMPs requires manufacturing technologies that can provide a robust backbone for phenotypic changes but also for increase in size. In this presentation a novel integrated and fully automated biomanufacturing platform will be showcased allowing the automated transition from single cells to organoids and finally to organoid-based 3D implants.

Amniotics has developed a MSC cell therapy for treatment of inflammatory lung diseases, currently tested in a Phase I clinical trial. The process uses multiple raw materials of biological origin, e.g., as source material (MSCs from amniotic fluid), sorting antibody, culture medium, detachment enzyme. Quality requirements, suitability for manufacturing of Phase I clinical material and supply issues are discussed here, as well as regulatory aspects and considerations for further development.

Cell and tissue banks are establishments adhering to strict quality management standards and regulations, and we advocate its prominent role to enhance the value of donated Substances of Human Origin in innovative Advanced Therapy Medicinal Products. To achieve this, we have created a platform for collaboration with academic and industrial developers, supporting a range of activities from bioprocess design and Good Manufacturing Practice validation, to early phase I/II clinical trials.

This work details a repeated batch process for reproducible expansion of pluripotent iPSCs in 3D with a closed seed train achieved using a hollow fibre bioreactor. This process was optimised using an acoustic filtration system to adapt the platform to perfusion. Perfusion processes demonstrate high yields of pluripotent iPSCs, with greater control of aggregate size. Ability to perform an integrated passage with equivalent growth profile allows for further intensification potential.

CAR T cell therapy success in solid tumors has been limited due to the lack of tumor-specific antigens, to tumor heterogeneity, and to the immuno-inhibitory nature of the tumor microenvironment. To address these challenges, we engineered CAR T cells that use the tumor-specific mesothelin antigen as a discriminatory target and have enhanced therapeutic properties provided by multiple attributes. Its manufacturing method has been designed using a representative small-scale model that led to a new large-scale workflow.

Cryopreservation of iPS cells in large numbers or of functional, differentiated cells is also crucial for later success in therapy or other applications. Therefore, to meet the increasing demand in downstream applications, we have established robust, scalable cryopreservation protocols for iPS cells and several derivatives. This includes the use of large volume cryobags, ready-to-use formats and cryopreservation of tissue engineered products.