The unique advantages exhibited by microgravity in enhancing the biological and chemical interactions for cells and tissues have come into greater focus following a quarter century of biological investigation aboard the International Space Station (ISS) in low earth orbit (LEO). One of its primary biomedical research purposes has been to investigate and mitigate the health risks faced by astronauts during prolonged spaceflight. However, as this status report describes, the hundreds of experiments aboard the ISS have also produced a vast quantity of knowledge opening up new possibilities for improving therapeutic modalities for the unmet medical needs of patients on earth. Among its many functions and capabilities, the ISS has been a preeminent biomedical research laboratory for biotechnology and drug development. Public-private partnerships have created the necessary collaborations and supplied the resources to conduct sophisticated biomedical experiments which have led to the improvement in the applications of stem cell biology, gene therapies, tissue engineering, and regenerative medicine. Technological advancements have also resulted in 3D bio printing of soft tissues such as blood vessels and micro physiological systems (Tissue on a Chip) using cells organized in a predetermined architecture. Nanomaterials assembled in microgravity formed with increased homogeneity and bioactivity can function as delivery platforms for cancer therapeutics or may be shaped into extracellular matrix supporting tissue regeneration therapies. Given these exciting innovations, and with the expectation that a robust regulatory framework will emerge, sustainable biomanufacturing in LEO is poised to unlock a transformative economic potential and accelerate the development of advanced next-generation therapeutics.
Alzheimer's disease (AD) significantly burdens global healthcare systems given limited treatment options to delay or stop disease progression. Chimeric antigen receptor (CAR) T cell therapy, an immunotherapeutic approach that has produced remarkably effective responses in cancer, offers a potential avenue for the treatment of AD. Here, we discuss three significant challenges of adapting CAR-T cell therapy for AD: (i) identifying a suitable antigen target; (ii) limited permeability of the blood-brain barrier; and (iii) long-term persistence and durability of manufactured CAR-T cell products. Potential strategies to overcome these hurdles provide an attractive opportunity to revolutionize the treatment for AD and potentially other neurodegenerative disorders.
Exploiting the therapeutic use of exosomes could revolutionize the pharmaceutical industry, by addressing major challenges such as enabling successful drug delivery to multiple tissues in a way that has a low immunogenicity profile and that allows repeat dosing. Exosomes are small, lipid-bound vesicles released by most if not all cell types. They play an array of biological roles and can carry a variety of cargo, which can be delivered into the cytoplasm of recipient cells. As ‘nature’s delivery vehicle’ they can be engineered to carry different kinds of therapeutic cargo, from RNA to proteins and even viruses. At Evox, we are addressing many of the challenges of harnessing exosomes as therapeutics by optimizing them to maximize loading of a range of drug cargoes, by scaling up the consistent manufacturing of these exosomes, and by also engineering exosomes to specifically target cell types and surmount normally restricted biological and physiological barriers.
Rupa Pike, PhD is the Senior Director of Technical Affairs for Advanced Therapies, Pharma Services Group at Thermo Fisher Scientific. The Office of Technical Affairs comprises scientific experts that serve as a strategic, innovational and educational leaders in the area of cell-based therapies, plasmids and mRNA therapeutics. In her prior role as the Director of Enterprise Science and Innovation Partnerships, she developed and managed strategic partnerships with global BioPharma, Biotech and Healthcare customers in the area of Cell and Gene Therapy. Prior to this, she was the Head of Technical Operations (Patheon/Thermo Fisher Scientific) where she worked closely with customers to conduct technology transfer and process optimization activities related to GMP manufacturing of cell-based therapies. She has over 15 years of expertise in GMP manufacturing and has successfully led GMP operations, Process Development and MSAT activities, infrastructure buildout, customer relations and business development.Delara Motlagh, PhD the General Manager of Cell Therapy Technologies at Terumo Blood and Cell Technologies, headquartered in Lakewood, Colorado. She is passionate about the cell & gene therapy market and the potential these innovative therapies hold to improve the lives of patients.She brings more than 18 years of experience in biotechnology and healthcare in various therapeutic areas including oncology, cardiology, orthopedics, hematology, and nephrology. Prior to joining Terumo Blood and Cell Therapies in 2017, Delara served in diverse leadership roles at Baxter Healthcare in marketing, research & development, and operations. Her cross-functional background provides a unique perspective and deep understanding of development, cell manufacturing, and commercialization elements in the industry. Delara received a PhD in Physiology and Biophysics from the University of Illinois, fellowship in Vascular Tissue Engineering at Northwestern University, and Executive MBA from Kellogg School of Management.Patrick Hanley, PhD is the Chief and Director of the Cellular Therapy Program and an associate professor of pediatrics at Children’s National Hospital and the George Washington University, respectively. He oversees processing for standard of care stem cell transplantation as well as the development, manufacture, quality, and testing of novel cellular therapies and is responsible for seeking partnerships and commercialization of promising cell and gene therapies. Trained as an Immunologist, Dr Hanley has an extensive background and interest in cellular therapy and is passionate about improving regulations for cellular therapy, training the next generation of cell therapists, and facilitating the translation of new therapeutics. Over the past 15 years he has helped to translate more than 300 products on over 25 cell therapy protocols – ranging from mesenchymal stromal cells to cord blood virus-specific T cells and tumor-associated antigen specific T cells – into the clinic.
Demand for gene therapies capable of treating previously inaccessible targets has risen precipitously in the past decade. Adeno-associated viruses (AAVs) are the preferred vector for gene delivery because of their favorable safety profile and tissue tropism, but they have significant manufacturing challenges, with end-to-end yields as low as 10-30%. To combat these low yields, we developed IsoTag™AAV, a novel purification technology for AAV that is a departure from the chromatographic paradigm in downstream processing. This proprietary technology uses a self-scaffolding recombinant protein reagent that can improve manufacturing yields. It enables purification by cost-effective and scalable filtration processes and improves product quality with minimal optimization. Herein, we describe the development of IsoTag™AAV, provide a head-to-head comparison to industry-leading affinity chromatography (evaluation carried out through a joint research project with Capsida Biotherapeutics), and demonstrate how it can reduce cost of goods for a clinical AAV program by 25%.
Spectrophotometric analysis is one of the most common techniques used to quantitate nucleic acids in a solution. More specifically, the 260/280 UV absorbance ratio of the nucleic acid can be used to determine their purity [1]Huss VAR, Festl, H, Schleifer KH. Studies on the spectrophotometric determination of DNA hybridization from renaturation rates. Syst. Appl. Microbiol. 1983; 4(2), 184–192. . However, traditional fixed-pathlength spectrophotometers have limitations when determining the purity ratios of these molecules. In this study, the CTechTM SoloVPE® system assessed theoretical DNA purity ratios by utilizing its variable pathlength method, known as Slope Spectroscopy®. The method was evaluated by assessing the specificity, intermediate precision, repeatability, linearity, and accuracy of the theoretical purity ratios. The observed purity ratios from the SoloVPE system demonstrated great comparison to the theoretical purity ratios, verifying the SoloVPE system’s slope spectroscopy method to be preferable for this application.
Gene engineering of immune cells is a powerful tool for creating advanced and novel cellular therapies.Currently, the critical step of cellular gene editing is primarily performed using virus-based gene delivery systems.Virus-based engineering methods are commonly plagued with long lead times, inconsistent batches, low cargo capacity, and high costs.Recently, advances in the non-viral transposon-based gene engineering have provided developers with an alternative gene engineering method that addresses virus-based platform limitations.Utilizing a 'cut-and paste' method of gene delivery, transposon-based systems are capable of stable genomic integration.This article discusses the transposon-based TcBuster™ platform, and its competitive advantages in cell and gene engineering.
With the increased number of therapeutic rAAV candidates reaching the clinical trial pipe-line, there is demand for innovative technologies to improve process development and facilitate manufacturing scale-up for future commercialization. To this end, Polyplus-transfection has worked hand-in-hand with viral vector manufacturers to develop a transfection re-agent specifically for large scale manufacturing in suspension cell systems: FectoVIR ® -AAV. FectoVIR ® -AAV aims to improve rAAV manufacturing processes by boosting productivity, bringing flexibility and facilitating scalability. Here, we share preliminary data from Allergan Biologics’ recent evaluation of FectoVIR ® -AAV against their current AAV production platform. Analysis of physical titers revealed a 3-fold increase in both viral particles (VP) and viral genome (VG) per ml of cell culture when using FectoVIR ® -AAV transfection reagent compared to PEIpro ® .
One of the major challenges of mRNA based vaccines has been their requirement for distribution and storage at extremely low temperatures, indicating that exposure of mRNA to suboptimal physico-chemical conditions can result in degradation and loss of potency; it is unclear whether this is due to instability of mRNA drug substance, or LNP-encapsulated mRNA, or both. In this study we compare the stability of model mRNA drug substance (eGFP, 995 nt) prepared by affinity chromatography with the stability of mRNA purified by precipitation. We show that both purification methods lead to highly pure mRNA drug substance, however, mRNA purified by chromatography remains stable for 28 days at 37°C, whereas mRNA purified by precipitation is subject to significant degradation under the same storage conditions. We conclude that chromatography eliminates elements and/or conditions with adverse impact on the quality of mRNA to a greater extent than precipitation method and that choosing appropriate purification strategy is crucial not only to achieve target purity but also to obtain a stable product with retained integrity.
Andy Case is a Supply Chain and Supply Chain Technology professional in the Bio-Pharmaceutical space. He is a subject matter expert in Chain of Identity and Chain of Custody for individualized cell therapies and the orchestration platforms designed to control COI/COC and supply chain activities for these therapies. Andy worked for four years at Novartis as Sr. Director of Supply Chain Technology and as a member of the team that launched Kymriah as the System Owner for CellChain the orchestration platform established by Novartis for its Cell and Gene therapies business. He is currently Head of Clinic Supply Chain, Individualized Therapies at Genentech/Roche where he is establishing supply chain capabilities for a portfolio of individualized therapies in clinical development. Andy has a BS in Civil Engineering from Texas A&M University and an MBA from IMD in Lausanne, Switzerland.
Watch the video or read the poster to learn: * Novel three-step purification process for plasmid (p)DNA * A new high productivity multimodal resin designed specifically for pDNA purification * Comparison between legacy and novel purification process in terms of productivity * How a novel fibro format could offer even greater productivity gains in the future Henrik Ihre has his roots in biopharma, leadership and product development for the biopharma downstream industry in specific. He is motivated by bringing new solutions and manufacturing of new pharmaceuticals for patients developed by partners of Cytiva. He has been the Director of Strategic Technologies since March 2020 with specific knowledge and background in the downstream purification of biopharmaceuticals for over 20 years.
Point-of-care (POC) manufacture can be defined as the production of therapies in clinical settings or units close to hospitals and patients. This approach is becoming increasingly viable due to the emergence of flexible manufacturing technologies. Expecting an increase in this kind of production, the UK’s regulatory agency, the Medicines and Healthcare products Regulatory Agency (MHRA) is proposing a regulatory framework specifically designed for POC manufacture. To discuss the challenges of POC manufacture and the MHRA’s proposal, the EPSRC Future Targeted Healthcare Manufacturing Hub (FTHMH) organized a workshop drawing insights from specialists in cell and gene therapy manufacture. Through presentations and discussion roundtables, the workshop highlighted the challenges for the UK and other countries implementing POC manufacture. The workshop attendees stressed four main issues: quality control; standardization and equipment use; availability of qualified personnel; and the challenges to be met by hospitals participating in POC manufacture systems. This commentary provides a summary of the points discussed in this workshop.
