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Automated Expansion of Primary Human T Cells in Scalable and Cell‐Friendly Hydrogel Microtubes for Adoptive Immunotherapy
Author(s) -
Lin Haishuang,
Li Qiang,
Wang Ou,
Rauch Jack,
Harm Braden,
Viljoen Hendrik J.,
Zhang Chi,
Wyk Erika,
Zhang Chi,
Lei Yuguo
Publication year - 2018
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201701297
Subject(s) - adoptive immunotherapy , self healing hydrogels , immunotherapy , materials science , cell culture , cell therapy , mesenchymal stem cell , cancer research , cell , chemistry , microbiology and biotechnology , immunology , medicine , immune system , biology , polymer chemistry , genetics , biochemistry
Adoptive immunotherapy is a highly effective strategy for treating many human cancers, such as melanoma, cervical cancer, lymphoma, and leukemia. Here, a novel cell culture technology is reported for expanding primary human T cells for adoptive immunotherapy. T cells are suspended and cultured in microscale alginate hydrogel tubes (AlgTubes) that are suspended in the cell culture medium in a culture vessel. The hydrogel tubes protect cells from hydrodynamic stresses and confine the cell mass less than 400 µm (in radial diameter) to ensure efficient mass transport, creating a cell‐friendly microenvironment for growing T cells. This system is simple, scalable, highly efficient, defined, cost‐effective, and compatible with current good manufacturing practices. Under optimized culture conditions, the AlgTubes enable culturing T cells with high cell viability, low DNA damage, high growth rate (≈320‐fold expansion over 14 days), high purity (≈98% CD3+), and high yield (≈3.2 × 10 8 cells mL −1 hydrogel). All offer considerable advantages compared to current T cell culturing approaches. This new culture technology can significantly reduce the culture volume, time, and cost, while increasing the production.