Measuring melanoma-specific cytotoxic T lymphocytes elicited by dendritic cell vaccines with a tumor inhibition assay in vitro

J Immunother. 2005 Mar-Apr;28(2):148-57. doi: 10.1097/01.cji.0000154247.97254.ef.

Abstract

Improving cancer vaccines depends on assays measuring elicited tumor-specific T-cell immunity. Cytotoxic effector cells are essential for tumor clearance and are commonly evaluated using 51Cr release from labeled target cells after a short (4 hours) incubation with T cells. The authors used a tumor inhibition assay (TIA) that assesses the capacity of cytotoxic T lymphocytes (CTLs) to control the survival/growth of EGFP-labeled tumor cell lines. TIA was validated using CD8+ T cells primed in vitro against melanoma and breast cancer cells. TIA was then used to assess the CTL function of cultured CD8+ T cells isolated from patients with metastatic melanoma who underwent vaccination with peptide-pulsed CD34+ HPCs-derived DCs. After the DC vaccination, T cells from six of eight patients yielded CTLs that could inhibit the survival/growth of melanoma cells. The results of TIA correlated with killing of tumor cells in a standard 4-hour 51Cr release assay, yet TIA allowed detection of CTL activities that appeared marginal in the 51Cr release assay. Thus, TIA might prove valuable for measuring spontaneous and induced antigen-specific cytotoxic T cells.

Publication types

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

MeSH terms

  • Antigens, CD34 / biosynthesis
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines*
  • Cell Line, Tumor
  • Cell Proliferation
  • Chromium / metabolism
  • Chromium Radioisotopes
  • Coculture Techniques
  • Culture Media / pharmacology
  • Dendritic Cells / cytology*
  • Flow Cytometry
  • Green Fluorescent Proteins / metabolism
  • HLA-A Antigens / chemistry
  • HLA-A2 Antigen
  • Humans
  • K562 Cells
  • Melanoma / blood
  • Melanoma / immunology*
  • Melanoma / therapy*
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Monocytes / cytology
  • Peptides / chemistry
  • T-Lymphocytes / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • Time Factors

Substances

  • Antigens, CD34
  • Cancer Vaccines
  • Chromium Radioisotopes
  • Culture Media
  • HLA-A Antigens
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • Peptides
  • Chromium
  • Green Fluorescent Proteins