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Modified tumour antigen-encoding mRNA facilitates the analysis of naturally occurring and vaccine-induced CD4 and CD8 T cells in cancer patients
- Source :
- Cancer Immunology, Immunotherapy, Vol. 58, No 3 (2009) pp. 325-338
- Publication Year :
- 2008
-
Abstract
- 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.
- Subjects :
- CD4-Positive T-Lymphocytes
Cancer Research
Lung Neoplasms
CD8-Positive T-Lymphocytes/*metabolism
Neoplasms/*blood/*metabolism
CD8-Positive T-Lymphocytes
Peptides/chemistry
Epitopes/chemistry
Epitope
CD4-Positive T-Lymphocytes/*metabolism
Epitopes
Carcinoma, Non-Small-Cell Lung
Neoplasms
RNA, Messenger/*metabolism
Immunology and Allergy
Cytotoxic T cell
1306 Cancer Research
ddc:616
Carcinoma, Non-Small-Cell Lung/metabolism
biology
CD28
Antibodies, Monoclonal
medicine.anatomical_structure
Oncology
2723 Immunology and Allergy
2730 Oncology
T cell
Antigens, Neoplasm/chemistry/*metabolism
Immunology
Antibodies, Monoclonal/chemistry
610 Medicine & health
Streptamer
Major histocompatibility complex
Cancer Vaccines
Interferon-gamma
Antigen
Antigens, Neoplasm
Cell Line, Tumor
medicine
Humans
RNA, Messenger
Antigen-presenting cell
Interferon-gamma/metabolism
2403 Immunology
Models, Genetic
10032 Clinic for Oncology and Hematology
biology.protein
Cancer research
Lung Neoplasms/metabolism
Peptides
Subjects
Details
- ISSN :
- 14320851 and 03407004
- Volume :
- 58
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Cancer immunology, immunotherapy : CII
- Accession number :
- edsair.doi.dedup.....74d9b0ad1d76b22820e8f43e3d38fe25