Scientific article

Modified tumour antigen-encoding mRNA facilitates the analysis of naturally occurring and vaccine-induced CD4 and CD8 T cells in cancer patients

Published inCancer immunology and immunotherapy, vol. 58, no. 3, p. 325-338
Publication date2009

The development of effective anti-cancer vaccines requires precise assessment of vaccine-induced immunity. This is often hampered by low ex vivo frequencies of antigen-specific T cells and limited defined epitopes. This study investigates the applicability of modified, in vitro-transcribed mRNA encoding a therapeutically relevant tumour antigen to analyse T cell responses in cancer patients. In this study transfection of antigen presenting cells, by mRNA encoding the tumour antigen NY-ESO-1, was optimised and applied to address spontaneous and vaccine-induced T cell responses in cancer patients. Memory CD8+ T cells from lung cancer patients having detectable humoral immune responses directed towards NY-ESO-1 could be efficiently detected in peripheral blood. Specific T cells utilised a range of different T cell receptors, indicating a polyclonal response. Specific killing of a panel of NY-ESO-1 expressing tumour cell lines indicates recognition restricted to several HLA allelic variants, including a novel HLA-B49 epitope. Using a modified mRNA construct targeting the translated antigen to the secretory pathway, detection of NY-ESO-1-specific CD4+ T cells in patients could be enhanced, which allowed the in-depth characterisation of established T cell clones. Moreover, broad CD8+ and CD4+ T cell responses covering multiple epitopes were detected following mRNA stimulation of patients treated with a recombinant vaccinia/fowlpox NY-ESO-1 vaccine. This approach allows for a precise monitoring of responses to tumour antigens in a setting that addresses the breadth and magnitude of antigen-specific T cell responses, and that is not limited to a particular combination of known epitopes and HLA-restrictions.

  • Antibodies, Monoclonal/chemistry
  • Antigens, Neoplasm/chemistry/*metabolism
  • CD4-Positive T-Lymphocytes/*metabolism
  • CD8-Positive T-Lymphocytes/*metabolism
  • Cancer Vaccines
  • Carcinoma, Non-Small-Cell Lung/metabolism
  • Cell Line, Tumor
  • Epitopes/chemistry
  • Humans
  • Interferon-gamma/metabolism
  • Lung Neoplasms/metabolism
  • Models, Genetic
  • Neoplasms/*blood/*metabolism
  • Peptides/chemistry
  • RNA, Messenger/*metabolism
Citation (ISO format)
KNIGHTS, Ashley J. et al. Modified tumour antigen-encoding mRNA facilitates the analysis of naturally occurring and vaccine-induced CD4 and CD8 T cells in cancer patients. In: Cancer immunology and immunotherapy, 2009, vol. 58, n° 3, p. 325–338. doi: 10.1007/s00262-008-0556-8
Updates (1)
ISSN of the journal0340-7004

Technical informations

Creation04/23/2012 1:23:58 PM
First validation04/23/2012 1:23:58 PM
Update time03/14/2023 5:25:38 PM
Status update03/14/2023 5:25:38 PM
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