SBIR Phase II: Engineered Induced Thymic Epithelial Cells for Novel T Cell Immunotherapies

The broader impact of this Small Business Innovation Research (SBIR) Phase II project is the development of novel off-the-shelf immunotherapies for patients with advanced cancer and limited treatment options. This project is enabled by a proprietary platform technology developed in Phase I of the project for mass production of a cell-based treatment with substantial improvements in molecular and functional fidelity. This novel platform offers a scalable, renewable approach for developing cost-effective therapies for a broad community of patients, and addresses major pain points in current adoptive immunotherapy development by eliminating time consuming and labor-intensive manufacturing processes and reducing expensive treatment cost. These advantages may enable the company to excel in the $3.3 billion immunotherapy market. Once developed, the novel cell-based off-the-shelf cell-based immunotherapies can provide significant healthcare, social, and economic impacts, and advance the health and welfare of the American public. The proposed project aims to develop and validate a novel platform technology for the scalable generation of high quality, robust tumor-targeted induced naïve T cells for off-the-shelf anticancer therapies. This platform employs a proprietary method to generate induced pluripotent stem cells (iPSC)-derived thymic epithelial cells as a critical element to enable induced naïve T cell production. The scientific rationale derives from the natural biology of the Thymus, where the transition of immature T cells to naïve T cells requires interaction with thymic epithelial cells through a process called positive selection. This project focuses on demonstrating the in vivo anti-tumor efficacy of these induced naïve T cells. The selected cancer targets are CD19 for B cell malignancies and MAGE-A4 for solid tumors. Xenograft models with human cancer cell lines and immunodeficient mouse will be used in the assessment. Overall, this project aims to accom