ISSN:
1569-8041
Keywords:
cutaneous T-cell lymphoma
;
immunotherapy
;
peptide library
;
T-cell epitope
;
tumour-associated antigen
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Background:Mycosis fungoides is the most frequent T-cell lymphomaof the skin. Despite numerous attempts, no tumour antigens have yet beenidentified. Only in one case has an idiotype-derived peptide been found totrigger CTL of the respective patient. The identification of natural antigensrequires the cultivation of large amounts of tumour cells in vitro,which has been possible in two exceptional cases. The identification ofsynthetic epitopes for tumour-specific CTL with random peptide libraries canovercome this limitation and is a powerful tool for application in thedevelopment of immune therapies for a wide range of patients. Materials and methods:The critical amino acids for theconstruction of epitopes for the CTCL-specific CTL clone My-La CTL weredetermined with synthetic peptide libraries in positional scanning OX8 formatin a standard 61chromium release assay. Sixteen different peptidescould be synthesized from the combinatoric of these amino acids with thecanonical anchor amino acids for MHC binding. These peptides were tested fortheir capacity to stimulate My-La CTL and PBMC of an HLA-matched CTCL patient. Results:A synthetic epitope could be identified for My-La CTL,which was recognized in a HLA-restricted manner. The response towards thisepitope was comparable to the response towards their natural target My-La.Using these synthetic epitopes, T cells of a HLA-matched patient could beinduced in vitroand led to the establishment of different cell linesand clones. Some of these lines recognized the peptides as well as theallogenic but HLA-matched tumour cell line My-La, indicating that they arespecific for a naturally expressed tumour antigen. Conclusions:The identification of synthetic epitopes fortumour-specific CTL clones can be used for the development of vaccines forimmune therapies of cancer; such peptides can be applied inter-individually.Synthetic epitopes must not correspond to the natural ones, but they can beeven more potent as stimulation of specific T cells and can be fine-tuned toincrease the success of the therapy.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1008395812464
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