Automated Expansion of Primary Human T Cells in Scalable and Cell-Friendly Hydrogel Microtubes for Adoptive Immunotherapy

Haishuang Lin, Qiang Li, Ou Wang, Jack Rauch, Braden Harm, Hendrik J. Viljoen, Chi Zhang, Erika Van Wyk, Chi Zhang, Yuguo Lei

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number1701297
JournalAdvanced Healthcare Materials
Volume7
Issue number15
DOIs
StatePublished - Aug 8 2018

Keywords

  • 3D cultures
  • T cells expansion
  • adoptive immunotherapy
  • alginate hydrogel tubes

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Pharmaceutical Science

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