TY - JOUR
T1 - Automated Expansion of Primary Human T Cells in Scalable and Cell-Friendly Hydrogel Microtubes for Adoptive Immunotherapy
AU - Lin, Haishuang
AU - Li, Qiang
AU - Wang, Ou
AU - Rauch, Jack
AU - Harm, Braden
AU - Viljoen, Hendrik J.
AU - Zhang, Chi
AU - Van Wyk, Erika
AU - Zhang, Chi
AU - Lei, Yuguo
N1 - Publisher Copyright:
© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2018/8/8
Y1 - 2018/8/8
N2 - 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 × 108 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.
AB - 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 × 108 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.
KW - 3D cultures
KW - T cells expansion
KW - adoptive immunotherapy
KW - alginate hydrogel tubes
UR - http://www.scopus.com/inward/record.url?scp=85046813730&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85046813730&partnerID=8YFLogxK
U2 - 10.1002/adhm.201701297
DO - 10.1002/adhm.201701297
M3 - Article
C2 - 29749707
AN - SCOPUS:85046813730
SN - 2192-2640
VL - 7
JO - Advanced Healthcare Materials
JF - Advanced Healthcare Materials
IS - 15
M1 - 1701297
ER -