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 accomplish two objectives: 1) increase efficacy of iPSC-derived T cell therapy relative to current approaches; and 2) reduce the prohibitively high cost of current autologous T cell therapies, advancing health equity for cancer patients. The resulting product may enable a significant advance in the development of iPSC-based T cell immunotherapies with clinically relevant cell fidelity, reproducibility and scalability.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

Award Number: 2451182
Principal Investigator: Hui Gai
Funds Obligated: $1,250,000
State: CA