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CD4+ T-cell recognition of human 5T4 oncofoetal antigen: implications for initial depletion of CD25+ T cells.
- Source :
-
Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2008 Jun; Vol. 57 (6), pp. 833-47. Date of Electronic Publication: 2007 Nov 15. - Publication Year :
- 2008
-
Abstract
- Background: The human 5T4 (h5T4) oncofoetal antigen is expressed by a wide variety of human carcinomas including colorectal, ovarian, gastric and renal, but rarely on normal tissues. Its restricted expression on tumour tissues as well as its association with tumour progression and bad prognosis has driven the development of a MVA-based vaccine (TroVax) which has been tested in several early phase clinical trials and these studies have led to the start of a phase III trial in renal cell carcinoma patients. We have recently shown that CD8(+) T cells recognizing h5T4 can be generated in the absence of CD4(+) T cells from peripheral blood lymphocytes of human healthy individuals.<br />Results: We report the existence and expansion of human CD4(+) T cells against h5T4 by stimulation with autologous monocyte-derived dendritic cells infected with a replication defective adenovirus encoding the h5T4 cDNA (Ad-h5T4). The h5T4-specific T-cell responses in normal individuals are enhanced by initial depletion of CD25(+) cells (putative T regulatory cells) prior to the in vitro stimulation. We have identified a novel h5T4-derived 15-mer peptide recognized by CD4(+) T cells in HLA-DR4 positive healthy individuals. Interestingly, CD4(+) T cells spontaneously recognizing a different 5T4 epitope restricted by HLA-DR were identified in tumour-infiltrating lymphocytes isolated from a regressing renal cell carcinoma lung metastasis.<br />Conclusion: Our data show that CD4(+) T cells recognizing h5T4 can be expanded and detected in healthy individuals and a renal cell carcinoma patient. Such h5T4-specific CD4(+) T cells boosted or induced by vaccination could act to modulate both cell or antibody mediated anti-tumour responses.
- Subjects :
- Antibodies chemistry
CD4-Positive T-Lymphocytes cytology
CD8-Positive T-Lymphocytes cytology
CD8-Positive T-Lymphocytes immunology
Carcinoma, Renal Cell immunology
Carcinoma, Renal Cell therapy
Dendritic Cells cytology
Epitopes chemistry
HLA-DR Antigens chemistry
Humans
Kidney Neoplasms immunology
Kidney Neoplasms therapy
Lymphocytes cytology
Models, Biological
Monocytes cytology
Monocytes metabolism
Tissue Distribution
Antigens, Neoplasm chemistry
CD4-Positive T-Lymphocytes immunology
Carcinoma, Renal Cell blood
Interleukin-2 Receptor alpha Subunit biosynthesis
Kidney Neoplasms blood
Subjects
Details
- Language :
- English
- ISSN :
- 0340-7004
- Volume :
- 57
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Cancer immunology, immunotherapy : CII
- Publication Type :
- Academic Journal
- Accession number :
- 18004564
- Full Text :
- https://doi.org/10.1007/s00262-007-0419-8