Enabling GMP-ready cell sorting for cell and gene therapy manufacturing

Knowing thyself: an audit of cell therapy manufacturing in Australia and New Zealand

Demand for cell and gene therapy treatments continues to outstrip supply, with only a small portion of eligible patients receiving cell and gene therapeutic treatment, such as CAR-T cell cancer therapy — in part, due to limited manufacturing capacity and high costs. Scaling up both manufacturing programs and processes of gene and gene-modified cell therapies in preparation for IND filing presents significant challenges, from transitioning through discovery and clinical phases to achieving GMP-compliant commercialization. Open systems, manual processes, and contamination risks often complicate the process, making early consideration of scalability essential to avoiding delays and costly adjustments. This infographic provides expert tips and key considerations for developing a scale-up or scale-out strategy in cell and gene therapy manufacturing, to bring these transformative therapies to more patients in need.

Particulates in CGT Guidance Survey Results – Cell and Gene Therapy Industry Knowledge Awareness

Acoustic Affinity Cell Selection: a non-paramagnetic scalable technology for T cell selection from unprocessed apheresis products

Navigating the constantly evolving regulatory landscape in cell and gene therapy manufacturing can pose critical challenges for developers and manufacturers. Failure to meet requirements can significantly raise costs, motivating the implementation of robust, reproducible, and compliant processes.

The authors have disclosed no conflicts of interest. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

FDA-regulated research: cellular therapy considerations

Kim Watanabe, PhD is the General Manager, Site Head for Patheon Translational Services. As part of the pharma services contract development and manufacturing organizational arm of Thermo Fisher Scientific, she leads the newly launched business that provides discovery stage, clinically bound clients with molecular biology, viral vector, and cell therapy services for in vivo gene therapy and ex vivo modified cell-based therapy research applications. Since joining Thermo Fisher Scientific in 2016, she has held multiple roles with increasing responsibility in product management and business integration and development. Prior to her current tenure, she was a Senior. Global Product Manager at Irvine Scientific (now Fujifilm Irvine Scientific), where she focused on cell culture products to support cell therapy applications. She was a stem cell research scientist at ScienCell Research Laboratories. Dr. Watanabe was a postdoctoral scholar at the University of California, San Diego, and received her doctoral degree in microbiology from the University of Virginia, and her BSc in cell and structural biology from the University of Illinois at Urbana-Champaign.

Gene and Cell Therapy Funding Opportunities in Horizon 2020: An Overview for 2014–2015

Cancer is one of the world's most concerning health problems and poses many challenges in the range of approaches associated with the treatment of cancer. Current understanding of this disease brings to the fore a number of novel therapies that can be useful in the treatment of cancer. Among them, gene and cell therapies have emerged as novel and effective approaches. One of the most important challenges for cancer gene and cell therapies is correct monitoring of the modified genes and cells. In fact, visual tracking of therapeutic cells, immune cells, stem cells and genetic vectors that contain therapeutic genes and the various drugs is important in cancer therapy. Similarly, molecular imaging, such as nanosystems, fluorescence, bioluminescence, positron emission tomography, single photon-emission computed tomography and magnetic resonance imaging, have also been found to be powerful tools in monitoring cancer patients who have received therapeutic cell and gene therapies or drug therapies. In this review, we focus on these therapies and their molecular imaging techniques in treating and monitoring the progress of the therapies on various types of cancer.

Optogenetics: Controlling Cardiac Depolarization and Hyperpolarization Using Combined Cell and Gene Therapy and Light-Sensitive Proteins

Introducing a New ASGCT Forum for Publication of Methodology and Clinical Development in Gene, Cell, and Oligonucleotide Therapies

In recent years, chimeric antigen receptor T (CAR-T) cells have shown significant promise in treating a range of cancers, with a number of approved products currently on the market. This has led to significant interest in optimizing cell therapy design and manufacturing. Traditionally, CAR-T cells are transfected expanded, and partially characterized before infusing into patients. However, the ability to predict in vivo efficacy is still challenging. Bioenergetic metabolism has been extensively linked to immune cell function and therefore represents a key attribute to be assessed during T cell therapy optimization and production. In addition, metabolic reprogramming can represent a mechanism to drive a desired immune phenotype. Agilent Seahorse XF T cell Metabolic Profiling kit is a robust new solution that combined with the Seahorse XF analyzer, allows for the simultaneous measurement of basal metabolic requirements, metabolic poise and mitochondrial bioenergetic capacity in T cells. These parameters have been shown to correlate with increased T cell persistence and improved metabolic fitness in nutrient restricted environments. This assay incorporates an improved uncoupler (BAM15) to allow more robust measurements of mitochondrial T cell bioenergetic capacity (measured as spare respiratory capacity or maximum respiration) with minimum optimization compared to uncouplers previously utilized. The XF T cell Metabolic Profiling kit has been used to evaluate the influence of expansion media composition on the metabolic phenotype of expanded human T cells. Indeed, when human T cells were activated and expanded up to 22 days in different commercial culture media formulations supplemented with different cytokine combinations, it resulted in T cell populations with differential bioenergetic profiles and mitochondrial spare capacities. These different metabolic phenotypes also correlated with different functional markers that have previously been associated with increased persistence in vivo. Similarly, the XF T cell Metabolic Profiling kit was used to assess metabolic poise and bioenergetic capacity of activated T cells under altered or restricted metabolic conditions like the ones present in the tumor microenvironment (low glucose, low glutamine), therefore allowing for better understanding of the effect of carbon source depletion during T cell stimulation. In addition, this assay coupled to the existing XF Hu T cell activation assay allowed for the assessment of T cell ‘fitness’ after re-stimulation in nutrient limited conditions. Taken together, the XF T cell Metabolic Profiling kit is a novel solution that provides a complete insight into the metabolic state of T cells in real-time, facilitating the evaluation of cell therapy expansion conditions and metabolic fitness of T cells under limited nutrient availability, which can be used to better design T cell therapies. Citation Format: Jessica Walls, Yoonseok Kam, Natalia Romero. A novel solution to assess T cell metabolic phenotype for the optimization of antitumor T cell therapy products [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2849.

Expanded Opportunities for Methods and Clinical Development

After an injury, axons in the central nervous system do not regenerate over large distances and permanently lose their connections to the brain. Two promising approaches to correct this condition are cell and gene therapies. In the present work, we evaluated the neuroprotective and neuroregenerative potential of pigment epithelium-derived factor (PEDF) gene therapy alone and combined with human mesenchymal stem cell (hMSC) therapy after optic nerve injury by analysis of retinal ganglion cell survival and axonal outgrowth. Overexpression of PEDF by intravitreal delivery of AAV2 vector significantly increased Tuj1-positive cells survival and modulated FGF-2, IL-1ß, Iba-1, and GFAP immunostaining in the ganglion cell layer (GCL) at 4 weeks after optic nerve crush, although it could not promote axonal outgrowth. The combination of AAV2.PEDF and hMSC therapy showed a higher number of Tuj1-positive cells and a pronounced axonal outgrowth than unimodal therapy after optic nerve crush. In summary, our results highlight a synergistic effect of combined gene and cell therapy relevant for future therapeutic interventions regarding optic nerve injury.