Poster Presentation Eradicate Cancer 2018

Melt electrospun 3 D lattices for the clinical scale expansion of immunomodulatory cells including human regulatory T cells (Tregs)   (#101)

Baggy Gundsambuu 1 , Katie Lowe 1 , Elena M De-Jaun Pardo 2 , Bahman Delalat 3 , Frances Harding 3 , Antonio SImula 4 , Justin Coombs 4 , Nico H Voelcker 3 , Dietmar w Hutmacher 2 , Simon C Barry 5
  1. Robinson Research Institute, North Adelaide, SA, Australia
  2. Institute for Health and Biomedical Innovation, Brisbane, Qld, Australia
  3. Future Industries Institute, University of South Australia, Adelaide, SA, Australia
  4. CRC for Cell Therapy manufacturing, Adelaide, sa, Australia
  5. RRI/WCHN, North Adelaide, SA, Australia

 

One of the most significant hurdles to the affordable, accessible delivery of cell therapy is the cost and difficulty of expanding cells to clinically relevant numbers. Immunotherapy to prevent autoimmune disease, tolerate organ transplants or target cancer critically relies on the expansion of specialised T cell populations. We have designed 3D-printed cell culture lattices with highly organized micron-scale architectures to bind monoclonal antibodies that trigger cell proliferation. This 3D technology platform facilitate the expansion of therapeutic human T cell subsets, including regulatory, effector, and cytotoxic T cells while maintaining the correct phenotype. This cell expansion platform is user-friendly and expedites cell recovery and scale-up, making it ideal for translating T cell therapies from bench to bedside.  Using an optimized cell handling protocol we are able to achieve over 200 fold expansion of human T cells in 14 days, and this yield is compatible with clinical dose numbers for cGMP manufacturing. In addition when the 3D lattice is used to grow regulatory T cells the activation and expansion environment favors FOXP3 expression compared with donor matched cultures with bead based expansion technology. The in vitro suppressor assay of these regulatory cells suggests that this enhanced FOXP3 expression is linked to increased potency. These data suggest that the quality of therapeutic T cells manufactured using 3D lattices may be enhanced, and this could result in more doses per batch, or fewer cells required per does. Both of which would have a positive impact on cots of goods.