Periodic Reporting for period 1 - STEPUP (Synthetic DCs for a T cEll ProdUction Platform)
Berichtszeitraum: 2017-11-01 bis 2019-04-30
Cancer immunotherapy has shown promising results in the treatment of cancer, with a wide variety of strategies, such as antibody therapy, now available to generate tumor-directed immune responses. Adoptive T-cell therapy is a therapy whereby T cells from patients are isolated, activated, (genetically) engineered, and expanded in order to be infused back into the patient for treatment. Chimeric antigen receptor T cell (CAR-T) therapy - T cells genetically engineered to express a receptor specific for certain tumors, has been the most successful adoptive treatment to date. CAR-T therapy has however, been hampered by efficacy issues (T cell persistence, functionality, targeting and exhaustion), as well as a time-consuming and expensive manufacturing process. In addition to the existing adoptive T cell therapies, artificial antigen presenting cells (aAPCs) are being developed as an alternative for efficient activation of T cells.
In the initial ERC project ‘PATHFINDER’, we developed aAPCs or synthetic dendritic cells (sDCs) based on highly flexible polyisocianide (PIC) polymers, that mimic naturally occurring DCs. The semi-flexible nature of the backbone polymer allows for proper arrangement and clustering of antigen and (co-)stimulatory receptors, a trait lacking in the existing reagents, resulting in potent activation and expansion of T cells. With the use of PIC-based sDCs, we proposed a production platform for tumour-specific T cells suitable for cancer immunotherapy. In this ERC PoC project, we further advanced the sDC technology, as well as examined the commercial potential and feasibility of this innovative approach for the ex-vivo activation and expansion of T cells as part of the CAR-T manufacturing process.
As part of our ERC PoC activities, we compared our sDCs against the current industry standard ex vivo activation and expansion reagents and generated data showing our platform has enhanced functionality over the current options (Proof of Principle). We also performed market analyses and stakeholder interviews that led to the identification of a primary beachhead market for the sDC technology (sDC Beads).Based on our Proof of Principle data and the manufacturing needs of industry, we prepared a business plan that outlines activities for the development, manufacturing and sale of products to meet industry’s needs for the ex-vivo expansion of immune cells (CAR-T, TCR, TIL, DC, etc.) for use in adoptive cell therapy. With the attached business plan, we believe we are well positioned to successfully transition our research to the commercial market.
In the initial ERC project ‘PATHFINDER’, we developed aAPCs or synthetic dendritic cells (sDCs) based on highly flexible polyisocianide (PIC) polymers, that mimic naturally occurring DCs. The semi-flexible nature of the backbone polymer allows for proper arrangement and clustering of antigen and (co-)stimulatory receptors, a trait lacking in the existing reagents, resulting in potent activation and expansion of T cells. With the use of PIC-based sDCs, we proposed a production platform for tumour-specific T cells suitable for cancer immunotherapy. In this ERC PoC project, we further advanced the sDC technology, as well as examined the commercial potential and feasibility of this innovative approach for the ex-vivo activation and expansion of T cells as part of the CAR-T manufacturing process.
As part of our ERC PoC activities, we compared our sDCs against the current industry standard ex vivo activation and expansion reagents and generated data showing our platform has enhanced functionality over the current options (Proof of Principle). We also performed market analyses and stakeholder interviews that led to the identification of a primary beachhead market for the sDC technology (sDC Beads).Based on our Proof of Principle data and the manufacturing needs of industry, we prepared a business plan that outlines activities for the development, manufacturing and sale of products to meet industry’s needs for the ex-vivo expansion of immune cells (CAR-T, TCR, TIL, DC, etc.) for use in adoptive cell therapy. With the attached business plan, we believe we are well positioned to successfully transition our research to the commercial market.