Generation of Tumor Antigen-Specific Cytotoxic T Lymphocytes from Pluripotent Stem Cells

Methods Mol Biol. 2019:1884:43-55. doi: 10.1007/978-1-4939-8885-3_3.

Abstract

Immunotherapy is a developing but very promising arsenal to treat cancer. Acquiring a more potent and effective approach in cancer immunotherapy is always the ultimate pursuance. CTL-based therapies are highly acclaimed recently due to its direct killing property. However, difficulty in obtaining adequate number of CTLs is still a major obstacle. In previous studies, it is shown that pluripotent stem cell-derived cytotoxic T lymphocytes (CTL)-especially the genetically engineered tumor antigen-specific CTLs-may serve as a good candidate for this goal. Here we introduce a novel approach in generating tumor antigen-specific CTLs from induced pluripotent stem cells (iPSCs) by using both in vitro and in vivo priming mechanisms for the tumor management in a murine melanoma model.

Keywords: Cytotoxic T lymphocytes; Immunotherapy; Melanoma; Notch signaling; Pluripotent stem cells.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / metabolism
  • Calcium-Binding Proteins
  • Cell Culture Techniques / instrumentation
  • Cell Culture Techniques / methods*
  • Cell Differentiation / immunology
  • Cell Line, Tumor
  • Female
  • Immunotherapy, Adoptive / methods*
  • Induced Pluripotent Stem Cells / physiology
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / immunology
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / immunology
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Intramolecular Oxidoreductases / immunology
  • Intramolecular Oxidoreductases / metabolism
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / pathology
  • Melanoma, Experimental / therapy
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • Skin Neoplasms / immunology
  • Skin Neoplasms / pathology
  • Skin Neoplasms / therapy
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism
  • T-Lymphocytes, Cytotoxic / transplantation

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, Neoplasm
  • Calcium-Binding Proteins
  • DLL4 protein, mouse
  • Dlk1 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Receptors, Antigen, T-Cell
  • Intramolecular Oxidoreductases
  • dopachrome isomerase