Abstract

T lymphocytes (T cells) play an important role in adoptive cellular immunotherapy (ACT). T cells can be stably derived and easily obtained by various methods of T cell development in vitro, which have more advantages than traditional methods of T cells isolated from autologous or allogeneic tissues. At present, there are mainly three methods for T cell development in vitro: fetal thymus organ culture, recombinant thymus organ culture and two-dimensional culture driven by Notch signal. Fetal thymus organ culture is easy to operate, the isolated thymus can support T cell differentiation and development to maturity in vitro, but the intact thymus has problems of limited maintenance time and difficulty in cell harvesting. In recombinant thymic organ culture, various thymic stromal cells are dispersed and recombined to construct a three-dimensional culture environment, which can support T cell maturation in vitro and in vivo; however, biomaterials and three-dimensional environment may lead to limited culture maintenance time and cell yield. Two-dimensional culture method uses artificial presentation of Notch signaling pathway ligands to drive T cell differentiation and development; the culture architecture is simple and stable, but it can only support T cell development to the early immature stage. This article reviews the research progress of various culture methods of T cell development in vitro, and discusses the existing problems and the future development to facilitate the application of ACT.

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