3D printed lattices as an activation and expansion platform for T cell therapy

Biomaterials. 2017 Sep:140:58-68. doi: 10.1016/j.biomaterials.2017.05.009. Epub 2017 Jun 7.

Abstract

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 specialized T cell populations. We have designed 3D-printed cell culture lattices with highly organized micron-scale architectures, functionalized via plasma polymerization 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. Lentiviral gene delivery to T cells is enhanced in the presence of the lattices. Incorporation of the lattice format into existing cell culture vessels such as the G-Rex system is feasible. 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.

Keywords: 3D lattice; Cell therapy manufacturing; Immunotherapy; Melt electrospin writing; Plasma polymer functionalization.

MeSH terms

  • Antibodies, Immobilized / pharmacology
  • Bioprinting / instrumentation
  • Bioprinting / methods
  • Cell Culture Techniques / instrumentation*
  • Cell Culture Techniques / methods
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Equipment Design
  • Humans
  • Immunotherapy, Adoptive
  • Printing, Three-Dimensional / instrumentation*
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / drug effects
  • Tissue Scaffolds / chemistry*

Substances

  • Antibodies, Immobilized