Tidal Therapeutics has developed a new technology that allows the generation of Chimeric Antigen Receptor-expressing T cells directly in vivo. The technology uses in vitro translated synthetic mRNA that is formulated in lipid nanoparticles. The LNPs are specifically targeted to circulating T cells to transiently express disease-specific receptors on the surface.

Cell therapy products tend to be novel and can be more complex compared to other biologics, presenting a number of analytical challenges. With few standardized methods available, we must be innovative and define our own best practices. Considerations for analytical development and for the characterization of cellular therapies will be discussed.

A handful of vendors now supply nearly every component necessary for bioprocessing – from designer cell lines and specialized media through bioreactors and columns. While these systems are presented as an ideal solution, designed to maximize yield, shorten the time, and simplify supply logistics, it is worthwhile to explore selecting and testing each component individually. Here we present work done by Sangamo’s process development team, increasing viral vector titers in bioreactors.

The purpose of this talk will be to walk through the design and build-out of a multi-product GMP manufacturing facility in an academic setting. The talk would review both the technical design considerations as well as business components to ensure staffing and Phase I compliance.

Natural killer (NK) cell infiltration into and anti-tumor immunity against solid tumors is often low. Functional and metabolic impairment of NK cells is induced by the suppressive microenvironment of solid tumors due to, among others, hypoxia, metabolites, such as adenosine, and the expression of inhibitory NK checkpoints. Here, we discuss our work in redirecting NK cells to overcome immunosuppressive solid tumor by genetically rewiring their functional and immunometabolic responses.

Human induced pluripotent stem cells (hiPSCs) have enormous promise to become breakthrough allogeneic treatments for numerous types of serious diseases. However, their potential can be bottlenecked due to unique challenges related to scalable manufacturing of high-quality hiPSCs for clinical and commercial purposes. PBS Biotech, with its innovative single-use bioreactors, provides scalable solutions to its global customers that enable them to scale up production of their therapeutic cells, with some entering various phases of clinical trials

Pluripotent Stem Cell (PSC)-derived cell therapies provide unprecedented opportunities to address unmet and seemingly intractable diseases. However, the development of cell therapy products derived from PSCs pose unique manufacturing challenges, including selection of starting cell lines, application of developmental biology, scaling, product profile, and cryopreservation. Here we will discuss these challenges and approaches to generate PSC-derived cardiomyocytes as a novel cell therapy to address heart failure.

• Overview of drug product development from formulation, fill-finish, and storage, to delivery  
• Formulation and process considerations to improve end-to-end drug product stability  
• Integrated drug product design to suit clinical and commercial supply chain needs​

We previously developed CD47-specific chimeric antigen receptor (CV1-CAR) T cells that overcome fratricide by downregulating CD47 expression. While CV1-CAR T cells are specific and exert potent antitumor activity in vitro, loss of cell surface CD47 prevented their persistence in vivo due to macrophage-mediated phagocytosis. Our results support current interests in CD47 overexpression to enhance adoptive cell transfer strategies.

Cell and gene therapy using viral vectors promises to overcome unmet needs in therapy of severe diseases. These viral vectors provide an analytical challenge during product development and stability assessment as they contain proteins, nucleic acids, and in some cases also a lipid membrane. The talk will provide an overview of latest analytical methods for virus particle characterization and show recent results from, e.g., analytical ultracentrifugation.

Conjugated peptide sequences redefine targeted delivery through their dual nature as both physical and informational constructs. Their physical properties are exploited through their gross electrochemical interactions with cellular structures, most notably the cell membrane. While their informational properties can be harnessed through the cell’s endogenous protein trafficking logic. We will discuss this utility and how to design and characterize their localization of drug actives to and even within organelle targets.