Ex vivo expansion of tumor specific lymphocytes with IL-15 and IL-21 for adoptive immunotherapy in melanoma

Cancer Lett. 2009 Nov 18;285(1):80-8. doi: 10.1016/j.canlet.2009.05.003. Epub 2009 Jun 6.

Abstract

Although T central memory cells have been described as the most effective T-cell subtype against tumor growth, little is known about the requirements needed for their optimal ex vivo generation. Hence, our goal is to establish a protocol that will lead to consistent ex vivo generation of lymphocytes skewed toward a central memory phenotype. Antigen-specific T-cell lines were generated by ex vivo stimulation with Class-I and Class-II melanoma peptide pulsed dendritic cells in the presence of either IL-2 or IL-15 plus IL-21. Tumor specific lymphocytes of both central memory and effector characteristics were consistently generated from healthy donors and melanoma patients. IL15/IL21 cultures result in a cell population with a lower proportion of CD4(+)CD25(high)FoxP3(+) regulatory cells and higher number of CD8(+) and CD56(+) cells, and consequently render a higher yield of cells with a greater cytolytic activity and IFN-gamma production against melanoma cell lines.

Publication types

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

MeSH terms

  • Antigens, Neoplasm / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD56 Antigen / analysis
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / transplantation
  • Case-Control Studies
  • Cell Proliferation*
  • Cells, Cultured
  • Dendritic Cells / immunology
  • Feasibility Studies
  • Forkhead Transcription Factors / analysis
  • Humans
  • Immunologic Memory*
  • Immunotherapy, Adoptive*
  • Interferon-gamma / metabolism
  • Interleukin-15 / metabolism*
  • Interleukin-2 / metabolism
  • Interleukin-2 Receptor alpha Subunit / analysis
  • Interleukins / metabolism*
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / transplantation*
  • Melanoma / immunology
  • Melanoma / pathology
  • Melanoma / therapy*
  • Melanoma-Specific Antigens
  • Neoplasm Proteins / immunology
  • Phenotype
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / transplantation*
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / transplantation

Substances

  • Antigens, Neoplasm
  • CD56 Antigen
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IL2RA protein, human
  • Interleukin-15
  • Interleukin-2
  • Interleukin-2 Receptor alpha Subunit
  • Interleukins
  • Melanoma-Specific Antigens
  • Neoplasm Proteins
  • Interferon-gamma
  • interleukin-21