Innovative Lipid-Based Delivery Solution: Unlocking New Opportunities in Manufacturing Genetically Modified Immune Cell Therapies

Gene-modified cell therapies, such as engineered T cells or Natural Killer (NK) cells expressing chimeric antigen receptors (CARs), are among themost promising treatments for cancer and autoimmune diseases. Traditionally, these therapies rely on lentiviral vectors to transfer the gene of interest; however, this approach is associated with lengthy manufacturing timelines, high costs, and potential safety risks. To overcome these limitations, our research focuses on lipid-based solutions as a promising alternative for producingCAR-T and CAR-NK cells. 

In this study, innovative lipid-based solution LipidBrick^® Cell Ready was employed first for transient protein expression with the production of functional ex vivomRNA-based CD19 CAR-T cells and then for stable cellmodification through the delivery of genetic engineering tools such as CRISPR using Cas9 mRNA and sgRNA targeting the TRAC gene. Optimization of T cell transfection was initially performed in 96-well plates before scaling up to a T25 flask. To demonstrate the versatility of this solution, diverse nucleic acid payloads (mRNA, plasmid DNA and nanoplasmid) and various cell types (T cells, NK cells, monocyte-derived dendritic cells and hematopoietic stem cells) were successfully transfected with our LipidBrick^® Cell Ready reagent. 

Finally, we’ve shown that our ready-to-use solution LipidBrick® Cell Ready could be efficient to generate functionalCD19 CAR-NK cells.