February 26, 2025 | 9am EDT

Bioengineering tools to enhance immune cell manufacturing and therapy 
Chimeric Antigen Receptor T cell (CAR-T) therapy is a breakthrough medicine that has revolutionized how cancer is treated. Nevertheless, CAR-T cell manufacturing faces challenges such as poor cell quality and low yield of transfected cells. In this talk, I will share two technologies that my lab has developed to deplete senescent immune cells to enhance cell quality for CAR-T therapy, and a high throughput nano-scale method (NExT) to transfect diverse immune cells with high efficiency.


Andy Tay
Presidential Young Professor @ National University of Singapore

February 26, 2025 | 11am EDT

Sensors and Control Strategies for Autologous CAR T-cell Production 

Patient specific, small-batch, custom CAR T-cell production requires new manufacturing methods to provide these transformative therapies more broadly and at acceptable costs. This webinar will cover two recent efforts from my research group to address this problem. First, the capability of reinforcement learning (RL), a subset of machine learning (ML), to control CAR T-cell activation by antigen-presenting beads and their subsequent expansion is explored in silico¹. The ‘digital twin’ environment is used to train RL-agents to dynamically control the number of beads in culture to maximize the population of robust effector cells for patient specific cells. Such a process could be implemented with dynamic imaging or other sensing modalities to track the cell state. In the second portion of the talk, single-use metabolite absorbing resonant transducer (SMART) sensors² are described for the dynamic monitoring of CAR T-cells during their expansion phase. Polyacrylate is shown to absorb secreted metabolites from living cells containing hydroxyl and alkenyl groups such as terpenoids, that act as a plasticizer. Upon softening, the polyacrylate irreversibly conformed into engineered voids above a resonant sensor, changing the local permittivity, which is interrogated, contact-free, with a vector network analyzer. Compared to sensing using the intrinsic permittivity of cells, the SMART approach yields a 20-fold improvement in sensitivity. The system has been validated with a wide range of production cell lines (E. coli, HEK, CHO) and production vessel types. Progress commercializing this technology and integrating these into next-generation G-Rex™ vessels (collaboration between Skroot Laboratory Inc. and Wilson Wolf Inc.) will also be highlighted.

1. https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/abs/10.1002/bit.28753
2. https://onlinelibrary.wiley.com/doi/full/10.1002/advs.202401260

Nigel Reuel
Associate Professor @ Iowa State University

February 26, 2025 | 1pm EDT

Machine-learning-guided quality control of CAR-T therapy product using microfluidic biophysical cytometry
Chimeric Antigen Receptor (CAR) T cell therapy is a revolutionary treatment for hematological malignancies. However, CAR T cell products exhibits significant variability in cell number, quality, and in vivo efficacy, which are caused by donor-specific cell quality as well as pre/post-manufacturing processes, including leukapheresis, cryopreservation and thawing procedures. This necessitates robust post-manufacturing and pre-infusion product testing. Here, we introduce a microfluidic, label-free approach to rapidly evaluate functional attributes of CAR T cells using biophysical features (size, deformability). Our biophysical assay correlates with phenotypic metrics, including CD4:CD8 ratio, memory subtypes, and cytotoxic activity. Validated across multiple donors and culture platforms, it requires fewer than 10,000 cells and delivers results within 10 minutes. Compared to labeled flow cytometry processing, the assay offers real-time data to guide adaptive manufacturing workflows. This is potentially a significant improvement and surrogate for existing phenotypic assessments, marking a step forward in advancing CAR T cell therapy manufacturing.

Jongyoon Han
Professor @ MIT

February 26, 2025 | 2:30pm EDT

Innovative scalable technologies for production of cell therapies 
Chimeric antigen receptor (CAR) T cell therapies have become an important tool for the treatment of hematological cancers. However, the manufacturing of CAR T therapies is a time-consuming multi-step process that requires isolation from the patient, activation, transduction, expansion, and autologous infusion. Due to the complex manufacturing steps, a single CAR T cell injection can cost more than $350k. There is a need to develop efficient and scalable processes to engineer T-cells in a cost-effective manner. Hydrogel coated membranes (HCMs) are tunable biomaterials that can be functionalized with a wide variety of antibodies to achieve T-cell activation. Additionally, the use of tangential flow filtration (TFF) can improve transduction efficiency with a CAR. In this work, a combination of HCMs and TFF was studied to improve T-cell activation and transduction. Primary CD3+ T-cells were activated using functionalized HCMs with ligands inspired by antigen-presenting cells. Phenotype and exhaustion markers were used to compare with industry standard TransAct, finding memory phenotype and minimal exhaustion with HCMs. The use of the TFF device with human Jurkat and primary CD3+ T-cells displayed significantly higher transduction compared to the static control, resulting in a lower required concentration of infectious units per cell. The combination of HCM activation and TFF device transduction presented in this work have the potential to improve current CAR T production, leading to enhanced phenotypes, improved throughput and scalability, and increasing accessibility to patients.

April Kloxin
Professor + Associate Chair of Chemical and Biomolecular Engineering @ Chemical and Biomolecular Engineering and Materials Science and Engineering, University of Delaware