Off-target toxicity due to the expression of target antigens in normal tissue represents a major obstacle to the use of chimeric antigen receptor (CAR)-engineered T cells for treatment of solid malignancies. To circumvent this issue, we established a clinical platform for engineering T cells with transient CAR expression by using in vitro transcribed mRNA encoding a CAR that includes both the CD3-ζ and 4-1BB co-stimulatory domains.

Redirecting T lymphocyte antigen specificity by gene transfer can provide large numbers of tumor-reactive T lymphocytes for adoptive immunotherapy. However, safety concerns associated with viral vector production have limited clinical application of T cells expressing chimeric antigen receptors (CAR). T lymphocytes can be gene modified by RNA electroporation without integration-associated safety concerns.

Next-generation non-viral RNA and DNA vectors have emerged as an attractive alternative for introducing CARs or TCRs into immune cells; while maintaining a high efficiency of delivery, they are more versatile and are simpler and quicker to manufacture at scale, thus increasing the number of patients who can be treated while significantly reducing the vein-to-vein time of the treatment process.