CD4+ T-cell recognition of human 5T4 oncofoetal antigen: implications for initial depletion of CD25+ T cells.
Affiliation
Department of Immunology, Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK. eelkord@picr.man.ac.ukIssue Date
2008-06
Metadata
Show full item recordAbstract
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. 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. 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.Citation
CD4+ T-cell recognition of human 5T4 oncofoetal antigen: implications for initial depletion of CD25+ T cells. 2008, 57 (6):833-47 Cancer Immunol. Immunother.Journal
Cancer Immunology, ImmunotherapyDOI
10.1007/s00262-007-0419-8PubMed ID
18004564Type
ArticleLanguage
enISSN
0340-7004ae974a485f413a2113503eed53cd6c53
10.1007/s00262-007-0419-8
Scopus Count
Related articles
- Induction of G250-targeted and T-cell-mediated antitumor activity against renal cell carcinoma using a chimeric fusion protein consisting of G250 and granulocyte/monocyte-colony stimulating factor.
- Authors: Tso CL, Zisman A, Pantuck A, Calilliw R, Hernandez JM, Paik S, Nguyen D, Gitlitz B, Shintaku PI, de Kernion J, Figlin R, Belldegrun A
- Issue date: 2001 Nov 1
- Unexpected abundance of HLA class II presented peptides in primary renal cell carcinomas.
- Authors: Dengjel J, Nastke MD, Gouttefangeas C, Gitsioudis G, Schoor O, Altenberend F, Müller M, Krämer B, Missiou A, Sauter M, Hennenlotter J, Wernet D, Stenzl A, Rammensee HG, Klingel K, Stevanović S
- Issue date: 2006 Jul 15
- Dendritic cells fused with allogeneic colorectal cancer cell line present multiple colorectal cancer-specific antigens and induce antitumor immunity against autologous tumor cells.
- Authors: Koido S, Hara E, Homma S, Torii A, Toyama Y, Kawahara H, Watanabe M, Yanaga K, Fujise K, Tajiri H, Gong J, Toda G
- Issue date: 2005 Nov 1
- In vitro stimulation of CD8 and CD4 T cells by dendritic cells loaded with a complex of cholesterol-bearing hydrophobized pullulan and NY-ESO-1 protein: Identification of a new HLA-DR15-binding CD4 T-cell epitope.
- Authors: Hasegawa K, Noguchi Y, Koizumi F, Uenaka A, Tanaka M, Shimono M, Nakamura H, Shiku H, Gnjatic S, Murphy R, Hiramatsu Y, Old LJ, Nakayama E
- Issue date: 2006 Mar 15
- Peptidome from renal cell carcinoma contains antigens recognized by CD4+ T cells and shared among tumors of different histology.
- Authors: Tassi E, Facchinetti V, Seresini S, Borri A, Dell'antonio G, Garavaglia C, Casorati G, Protti MP
- Issue date: 2006 Aug 15