TOPIC 414 : SYNTHETIC BIOLOGY GENE CIRCUITS FOR CANCER THERAPY

B-cell non-Hodgkin’s lymphoma (NHL) is the most common hematological malignancy derived from B-cells and expresses high levels of the CD19 antigen. Although past gene therapy efforts that target CD19, such as chimeric antigen T cell receptor (CAR-T) immunotherapy, have demonstrated immense clinical benefit, manufacturing challenges and toxicity have significantly limited its utility. To this end, Strand Therapeutics proposes the development of an universal off-the-shelf CAR-T CD19 circuit small molecule based on its proprietary self-replication mRNA (repRNA) platform. This approach is designed to illicit a targeted CD19 CAR-T response to B cell malignancies in situ with the incorporation of their patented drug delivery system to bypass toxicity. Specifically, to improve outcomes for patients with B cell NHL, Strand Therapeutics will develop a programmable mRNA gene circuit therapy that provides precise control of the dose and timing of the CD19 antigen in B-cell NHL tumors. At study completion, Strand will have validated the sustained and controlled expression and efficacy of the CAR-T CD19 cells in vivo and demonstrated decreased toxicty. These results will support GMP manufacturing and GLP-toxicology studies of the candidate molecule towards the eventual submission of an Investigational New Drug.