In Vitro Differentiation of T Cells from Murine Pluripotent Stem Cells

Methods Mol Biol. 2019;2048:131-141. doi: 10.1007/978-1-4939-9728-2_14.

Abstract

In recent years cancer immunotherapy, especially the cell-based immunotherapy, has reached several milestones and achieved a lot of cancer remission in the clinics. Obtaining a more potent and effective cytotoxic T lymphocytes (CTLs) for cancer immunotherapy is always the ultimate goal for the researchers. However, the difficulty in harvesting a large number of tumor antigen-specific CTLs from the tumor patient is still a major obstacle we need to overcome. In our previous studies, it is shown that pluripotent stem cell-derived CTL-especially the genetically engineered antigen-specific CTLs-may serve as a good source of unlimited number of highly reactive and antigen-specific CTLs. Here we present a two-step method for the generation of antigen-specific T lymphocytes from iPS cells by in vitro priming and in vivo maturation.

Keywords: Differentiation; Induced pluripotent stem cells; Notch signaling; Stem cell biology; T cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Cell Culture Techniques / instrumentation
  • Cell Culture Techniques / methods*
  • Cell Differentiation
  • Cell Line, Tumor
  • Coculture Techniques / instrumentation
  • Coculture Techniques / methods
  • Culture Media / metabolism
  • Disease Models, Animal
  • Female
  • Flow Cytometry / instrumentation
  • Flow Cytometry / methods
  • Genetic Vectors / genetics
  • Homeodomain Proteins / genetics
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Induced Pluripotent Stem Cells / physiology*
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / therapy*
  • Mice
  • Mice, Knockout
  • Protein Engineering / methods
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Retroviridae / genetics
  • T-Lymphocytes, Cytotoxic / physiology
  • T-Lymphocytes, Cytotoxic / transplantation*
  • Transduction, Genetic / instrumentation
  • Transduction, Genetic / methods

Substances

  • Antigens, Neoplasm
  • Calcium-Binding Proteins
  • Culture Media
  • Dlk1 protein, mouse
  • Homeodomain Proteins
  • Receptors, Antigen, T-Cell
  • Recombinant Proteins
  • RAG-1 protein