Research Objective: Bioengineering of artificial Antigen Presenting Cells, aAPCs, to enrich and expand target T cell populations, including scale-up using GMP-compliant approaches.

Technology Outcome: Next generation aAPC and T cell enrichment and expansion protocol using aAPCs.

The goal of TR&D 1 is to engineer novel artificial Antigen Presenting Cells (aAPCs) to optimize production of T cells for therapeutic uses such as adoptive immunotherapy. We will use nanoscale paramagnetic aAPCs coupled to our Enrichment and Expansion (‘E+E’) approach to simplify, streamline, and scale-up production of T cells for adoptive immunotherapy. This goal will be supported by four Specific Aims:

• Specific Aim 1: Enrichment+Expansion, E+E, of Tumor Antigen-Specific T Cells Using Nano-aAPCs: Addressing ACT barriers.
• Specific Aim 2: Development and Analysis of Class II-based aAPCs: Tapping CD4+ T cells for ACT
• Specific Aim 3: In Vivo Activity of Tumor Antigen-Specific T Cells in ACT.
• Specific Aim 4: Preparation for Translation.

The use of engineered nano-aAPCs coupled to E+E will increase control and scale-up of cellular therapies, which will enhance, expand, and accelerate clinical adoption and use. TR&D 1 will also demonstrate the breadth of nano-aAPCs coupled to E+E that will be used to target a variety of different antigen-specific responses. We anticipate that with completion of TR&D 1’s Preparation for Translation Specific Aim, we will have studied scale up for production of T cells in a GMP-compatible fashion by the end of the 5th year.