title: Improving T Cell Expansion with a Soft Touch.
abstract: 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+-only and mixed CD4+-CD8+T cell preparations. CD8+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.
authors.affiliation: Department of Biomedical Engineering, Columbia University , New York, New York 10027, United States.
authors.forename: Lester H
authors.initials: LH
authors.lastname: Lambert
authors.affiliation: Department of Biomedical Engineering, Columbia University , New York, New York 10027, United States.
authors.forename: Geraldine K E
authors.initials: GK
authors.lastname: Goebrecht
authors.affiliation: Department of Biomedical Engineering, Columbia University , New York, New York 10027, United States.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: De Leo
authors.forename: Roddy S
authors.initials: RS
authors.lastname: O'Connor
authors.forename: Selene
authors.initials: S
authors.lastname: Nunez-Cruz
authors.affiliation: Advanced Science Research Center of CUNY , New York, New York 10031, United States.
authors.forename: Tai-De
authors.initials: TD
authors.lastname: Li
authors.affiliation: Department of Biomedical Engineering, Columbia University , New York, New York 10027, United States.
authors.forename: Jinglun
authors.initials: J
authors.lastname: Yuan
authors.forename: Michael C
authors.initials: MC
authors.lastname: Milone
authors.affiliation: Department of Biomedical Engineering, Columbia University , New York, New York 10027, United States.
authors.forename: Lance C
authors.identifier: 0000-0001-6812-4956
authors.initials: LC
authors.lastname: Kam
mesh_terms: D000906:Antibodies / Q000737:chemistry; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D049109:Cell Proliferation; D002470:Cell Survival; D004129:Dimethylpolysiloxanes / Q000737:chemistry*; D004655:Emulsions; D006801:Humans; D007167:Immunotherapy; D008863:Microspheres; D010316:Particle Size; D013499:Surface Properties; D013601:T-Lymphocytes / Q000166:cytology* / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000502:physiology
chemical_list: D000906:Antibodies; D018106:CD28 Antigens; D017252:CD3 Complex; D004129:Dimethylpolysiloxanes; D004655:Emulsions; C013830:baysilon
keywords: T cell; immunotherapy; mechanobiology; nanoscale rigidity