CRISPR and human induced pluripotent stem cells (iPSCs) form a partnership that has fundamentally reshaped biomedical research. Together, they enable disease modeling, functional studies, and high-throughput screening in iPSC-derived systems.
Yet, with this powerful potential comes the challenge of maintaining rigor and reproducibility. iPSCs are uniquely sensitive, susceptible to pluripotency drift and genomic instability—a trait that becomes particularly obvious after gene editing. Ensuring reliability therefore depends on standardized methodologies and robust quality control, highlighting the critical role of core facilities. By providing expertise, optimized protocols, and stringent quality assurance, these facilities safeguard the integrity of research outcomes.
This talk will explore not only the groundbreaking opportunities offered by the CRISPR–iPSC combination, but also the essential quality measures required to ensure consistency, reliability, and reproducibility in the field.

Learning Objectives:

1. Describe how CRISPR and induced pluripotent stem cells (iPSCs) are applied in disease modeling, functional studies, and high-throughput screening.

2. Explain challenges such as pluripotency drift and genomic instability that affect iPSC research after gene editing.

3. Discuss how standardized methodologies, quality control measures, and core facilities support rigor and reproducibility in CRISPR–iPSC studies.

Despite remarkable success in relapsed or refractory B-cell malignancies, CAR T-cell therapy faces significant challenges: primary resistance, relapse, and treatment-related toxicities. This talk reviews clinical outcomes of FDA-approved CAR T products and highlights emerging mechanisms of resistance—including tumor-intrinsic factors such as CD58 loss, host microenvironmental barriers, and T-cell exhaustion. Dr. Ruella will present pre-clinical and clinical data on novel strategies to overcome these obstacles: engineering PD-1:intracellular-CD2 switch receptors to restore CD2–CD58 co-stimulation; leveraging metabolic modulation with the ketogenic diet and β-hydroxybutyrate to enhance CAR T oxidative phosphorylation and persistence; and applying CD5-knockout CAR T cells to treat T-cell lymphomas while preserving immune competence. Attendees will gain a translational perspective on next-generation CAR T design and how these innovations may broaden indications, improve durability of response, and reduce toxicity in hematologic cancers.

Learning Objectives:

1. Analyze clinical and biologic mechanisms that drive primary and acquired resistance to CAR T-cell therapy in B-cell malignancies.

2. Analyze clinical and biologic mechanisms that drive primary and acquired resistance to CAR T-cell therapy in B-cell malignancies.

3. Discuss translational approaches for expanding CAR T therapy to T-cell lymphomas and autoimmune diseases while mitigating toxicity.

From 12-1 PM PT on the day of the event, Labroots is excited to offer a variety of interactive networking opportunities designed to help you engage, explore, and expand your network.

Connect with fellow attendees in the social space through Speed Networking, chat with poster authors during our live Poster Discussion, and earn bonus points by visiting booths in our Exhibit Hall. See you there!

A fundamental challenge for cystic fibrosis (CF) gene therapy is ensuring sufficient transduction of airway epithelial cells to achieve therapeutic correction. Gene editing is a method to permanently correct pathogenic variants of the CFTR gene in airway epithelial cells. Our overall goal is to repair CFTR mutations that are unresponsive to modulator therapies, such as R553X and W1282X. Although CRISPR/Cas9 is a powerful gene editing tool, it requires a double stranded break of the genome. Adenine base editors (ABE) offer a safer approach by generating a single stranded break through the nickase activity of a deactivated Cas9 (dCas9)to convert an A>G nucleotide (present in all nonsense and many missense variants). Here we employ new editing tools delivered by a single AAV vector with enhanced tropism for airway epithelia in a G551D CF pig model. Although G551D is responsive to small molecule therapies, establishing gene editing proof of concept in a large animal model would widely advance applications of base editing tools, paving the way for other target mutations.   Recently, we made an exciting discovery that formulating viral vectors with hypertonic saline remarkably enhances gene transfer. Given the safety track record with inhaled hypertonic saline (3-7% NaCl), this is a formulation that could be immediately implemented in a clinical trial design. This simple, but innovative formulation increases ionic strength, enhances stem cell transduction, and improves overall delivery efficacy. Although G551D is a druggable mutation type, using this large animal model to establish proof of concept will advance our knowledge on the efficacy of base editing in vivo. This innovative work combines multiple factors including a base editor delivered by a single AAV vector, a boost in delivery using hypertonic saline, and a large animal model that recapitulates CF lung disease.

Learning Objectives:

1. Explain how adenine base editors (ABE) differ from CRISPR/Cas9 in their mechanism and potential safety advantages for correcting CFTR mutations.

2. Describe how a single AAV vector and hypertonic saline formulation enhance gene transfer and editing efficiency in airway epithelial cells.

3. Discuss the role of the G551D CF pig model in establishing proof of concept for base editing approaches in cystic fibrosis.

Lymphodepletion chemotherapy followed by infusion of T cells that are genetically modified to express a chimeric antigen receptor (CAR) targeted to CD19 is a novel therapy for patients with relapsed and/or refractory B cell malignancies.We conducted a series of phase 1/2 clinical trials in which CD19 CAR-T cells are manufactured from distinct subsets of T cells and formulated in a defined composition for infusion to patients with large B cell non-Hodgkin lymphoma. Outcomes of these studies and correlative research will be presented.

Learning Objectives:

1. Identify factors impacting outcomes of CD19 CAR-T for large B cell lymphoma

2. Discuss outcomes of a phase 1 trial combining exogenous IL-15 support with CD19 CAR-Ts for large B cell lymphoma

3. Identify insight into the impact of timing of anti-PD-L1 when combined with CD19 CAR-T for large B cell lymphoma

Human pluripotent stem cells (hPSCs) represent powerful tools for modelling early human embryogenesis and provide a source of differentiated cells for use in regenerative medicine. The assurance of genetic stability is essential for uses of hPSCs in basic research and regenerative medicine. Nonetheless, hPSCs are known to acquire non-random genetic changes, including recurrent aneuploidies. Some of the acquired genetic aberrations that are associated with the selective growth advantage of variant hPSCs are known to be associated with oncogenesis in other situations, raising the concern that they may also confer tumorigenic or malignant properties on either transplanted differentiated cells or left-over undifferentiated hPSCs. Moreover, genetic changes in hPSCs could also impact basic research because the experimental manipulation of aneuploid hPSCs possessing aberrant proliferation rates or varying differentiation abilities may generate unpredictable results, rendering hPSC-based disease modelling, and developmental studies unreliable.
In our work we are elucidating the molecular mechanisms that underlie the maintenance of the integrity of the hPSC genome, and how disruption of these mechanisms can lead to undesired genetic changes. We are also studying the functional effects of aneuploidy on the behavior of hPSCs in vitro. Our recent work has demonstrated that the dominance of aneuploid hPSCs in mosaic cultures is enhanced through competitive interactions resulting in elimination of wild-type cells, akin to the cell competition behavior described in other cell and developmental models. Understanding of the causes and consequences of aneuploidy in hPSCs will help inform approaches to minimise their occurrence in hPSC cultures destined for clinical or research use. These insights may be also pertinent to assisted conception efforts and may open new therapeutic approaches to target aneuploid cells in cancer.

Learning Objectives:

1. identify the types of genetic changes that commonly occur in hPSCs

2. appraise the key issues and challenges that genetic changes in hPSCs represent for regenerative medicine

3. discuss how understanding of the processes of mutation and selection may contribute to minimising the appearance of genetic variants