Search

Background & Aim Significant losses of bone tissues that are often too large to heal occur in >10% of all open fractures and present an urgent clinical challenge associated with grave morbidities and huge healthcare costs. Bone autografting, the therapeutic standard in such cases, has a 50% complication rate, with persistent infection or non-union present in 18% of the patients, and further surgery required in 36% of them. Bone tissue engineering technologies have been widely suggested as an alternative to autografts. Such technologies were tested in segmental animal bone defects up to 5 cm long, with success reported mostly for defects under 2.5 cm. This size (or equivalent product volume) is also the upper limit for tissue-engineered bone grafts in clinical development. Considering that much larger defects, with a mean of 5.5 cm, are encountered in the clinic, Bonus is developing autologous tissue-engineered bone grafts for the treatment of defects larger than 2.5 cm. Methods, Results & Conclusion Bonus utilizes proprietary procedures to isolate adipose tissue-derived mesenchymal cells from patients’ lipoaspirates, seed them on mineral scaffold particles, and culture them in a specially designed bioreactor (Fig. 1). The expansion of the cells on this scaffold increases their osteo-inducibility, allowing a controlled osteoinduction process that possibly also retains some of these cells’ additional regenerative functions. This possibility is exemplified by the higher levels of osteogenic and other genes related to angiogenesis and ECM remodeling expressed by 3D-osteoinduced cells, compared to the 2D ones. After their osteoinduction, the cells and scaffold are washed and formulated into the final product—BonoFill-II. In a preclinical study, BonoFill-II applied to a 3.2 cm defect in a sheep tibia led to a full recovery in 12 weeks (N=7), as well as a full bridging of a 10.5 cm defect (Fig. 2). A phase I/II clinical trial is currently underway testing BonoFill-II in patients with bone defects ≥2.5 cm. So far, we have treated patients with defects up to 8.5 cm long and a history of 2-7 failed prior interventions, with a few representatives that can exemplify this study safety and efficacy (Fig. 3). The performance of BonoFill-II was also tested in Phase I/II trial in patients in need of a bone transplant in the upper maxilla with complete success reported. Overall, the solid underlying science and innovative technologies developed by Bonus position BonoFill-II as a promising alternative to bone autografts.

Background & Aim The field of Adoptive Cell Therapies (ACT) is a an ever-evolving, fast-paced environment. In order to quickly advance translational research into viable commercial products, industry will need to partner closely with academic centers. Organizations such as Fred Hutch are well positioned to support these partnerships in a manner that quickly enables these products and technologies to rapidly advance from bench to bedside. By ensuring robust Process Development, Process Transfer, Clinical Manufacturing and Analytical Development, academic centers are able to provide the services and support required to quickly enable Phase I and II clinical trials. By leveraging existing infrastructure such as manufacturing cleanrooms and state-of-the-art clinics, industry partners are able to test a number of targets in order to identify the best candidates to bring forward to commercialization without the need for significant capital investments. Methods, Results & Conclusion This presentation will focus on the key aspects required for successful industry/academic partnerships. Starting with exploratory business development activities, academic centers must review the overall portfolio of IP existing within the academic center to best determine whether there is an opportunity to leverage existing technology or if a more traditional contract manufacturing and development opportunity would be a better solution. From there, the agreements, contracts, etc., help define the relationship and establish the method(s) of communication while also developing the key metrics used to determine success. We will explore the value of Process Development and Technology Transfer using the role of Process Engineers to ensure a robust manufacturing process is identified. Key attributes will be highlighted that ensure a successful partnership both within manufacturing and the clinic. Finally, an often-overlooked area of focus is the transfer of the technology back out to a Phase III or commercial manufacturer where registrational activities and future commercial manufacturing will take place.

Superparamagnetic iron oxide (SPIO) nanoparticles are being used for intracellular magnetic labeling of stem cells and other cells in order to monitor cell trafficking by magnetic resonance imaging (MRI) as part of cellular-based repair, replacement and treatment strategies. This review focuses on the various methods for magnetic labeling of stem cells and other mammalian cells and on how to translate experimental results from bench to bedside.

The National Institutes of Health (NIH) Department of Transfusion Medicine has supported clinical investigation in cellular therapies over the past 20 years. This experience, which encompasses product development research, quality system design and product manufacturing for a wide range of early phase clinical trials, provides a firm basis for future work with novel stem cell therapies.

While the technology of translational research is sometimes considered a poor relation to 'basic science', it has become a central focus of work to turn exciting new concepts into practical therapies. Here we use the example of selective T-cell depletion of allografted lymphocytes to illustrate the problems of scale-up, reproducibility, sterility, safety and regulatory concerns encountered during the bench to bedside process.

The field of cellular therapeutics has immense potential, affording an exciting array of applications in unmet medical needs. One of several key issues is an emphasis on getting these therapies from bench to bedside without compromising safety and efficacy. The successful commercialization of cellular therapeutics will require many to extend the shelf-life of these therapies beyond shipping "fresh" at ambient or chilled temperatures for "just in time" infusion. Cryopreservation is an attractive option and offers potential advantages, such as storing and retaining patient samples in case of a relapse, banking large quantities of allogeneic cells for broader distribution and use and retaining testing samples for leukocyte antigen typing and matching. However, cryopreservation is only useful if cells can be reanimated to physiological life with negligible loss of viability and functionality. Also critical is the logistics of storing, processing and transporting cells in clinically appropriate packaging systems and storage devices consistent with quality and regulatory standards. Rationalized approaches to develop commercial-scale cell therapies require an efficient cryopreservation system that provides the ability to inventory standardized products with maximized shelf life for later on-demand distribution and use, as well as a method that is scientifically sound and optimized for the cell of interest. The objective of this review is to bridge this gap between the basic science of cryobiology and its application in this context by identifying several key aspects of cryopreservation science in a format that may be easily integrated into mainstream cell therapy manufacture.