Cancer Immune Therapy Edited by G. Stuhler and P. Walden ...

Tab. 1.1. Publicly available alogorithms for epitope deduction
Algorithm Internet site
Tab. 1.2 Tumor-associated antigens with peptide
epitopes identified by the method of deduction
Antigen Reference
Ig idiotype 26
Telomerase hTERT 28
Survivin 47
Mage-3 48
P53 49
Ras 50
Bcr-abl 51
Proteinase-3 52
Wilm's tumor antigen-1 53
CEA 54
PSA 55
Her2-neu 56
MUC-1 57
Folate-binding protein 58
Ep-CAM 59
1.5 Epitope Deduction
BioInformatics & Molecular http://bimas.dcrt.nih.gov/molbio/hla_bind/
Analysis Section
SYFPEITHI http://www.uni-tuebingen.de/uni/kxi/
SEREX http://www-ludwig.unil.ch/SEREX/mhc_pep.html
candidate epitopes are used to generate specific CTLs that are then evaluated for cytotoxicity
against tumor cells expressing the antigen and the appropriate MHC allele.
A similar approach shows promise for the identification of MHC class II-restricted
epitopes [20].
In some cases, due to mutation, protein fusion or recombination, the deduced peptide
epitopes are truly tumor-specific. Typically, the antigen from which the epitope
is deduced is a self-protein, for which the existence of T cell tolerance may be formidable
[21, 22]. Tolerance is less probable against epitopes derived from oncogenic viral
proteins, but the clinical applicability of such deduced epitopes is restricted to a few
tumor types. For epitopes identified by deduction, we speculate that most ± but certainly
not all [23, 24] ± are probably ignored by the immune system, even in the setting
of measurable cancer, raising the hypothesis that targeting such epitopes might
draw upon a naÒve T cell repertoire that has been spared functional inactivation [18].
It is controversial how well HLA/peptide affinity is predicted by available algorithms
and whether or not this truly indicates immunogenicity. For some antigens, such as
human papillomavirus [25] or the human immunoglobulin idiotype [26], there is a
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