1 research outputs found
Improving T Cell Expansion with a Soft Touch
Protein-coated microbeads
provide a consistent approach for activating
and expanding populations of T cells for immunotherapy but do not
fully capture the properties of antigen presenting cells. In this
report, we enhance T cell expansion by replacing the conventional,
rigid bead with a mechanically soft elastomer. Polydimethylsiloxane
(PDMS) was prepared in a microbead format and modified with activating
antibodies to CD3 and CD28. A total of three different formulations
of PDMS provided an extended proliferative phase in both CD4<sup>+</sup>-only and mixed CD4<sup>+</sup>–CD8<sup>+</sup> T cell preparations.
CD8<sup>+</sup> T cells retained cytotoxic function, as measured by
a set of biomarkers (perforin production, LAMP2 mobilization, and
IFN-γ secretion) and an in vivo assay of targeted cell killing.
Notably, PDMS beads presented a nanoscale polymer structure and higher
rigidity than that associated with conventional bulk material. These
data suggest T cells respond to this higher rigidity, indicating an
unexpected effect of curing conditions. Together, these studies demonstrate
that adopting mechanobiology ideas into the bead platform can provide
new tools for T cell based immunotherapy