Improving T Cell Expansion with a Soft Touch

详细信息    查看全文

• 作者：Lester H. Lambert ; Geraldine K. E. Goebrecht ; Sarah E. De Leo ; Roddy S. O’Connor ; Selene Nunez-Cruz ; Tai-De Li ; Jinglun Yuan ; Michael C. Milone ; Lance C. Kam
• 刊名：Nano Letters
• 出版年：2017
• 出版时间：February 8, 2017
• 年：2017
• 卷：17
• 期：2
• 页码：821-826
• 全文大小：440K
• ISSN：1530-6992

文摘

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.