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

22 2 Serological Determinants On Tumor Cells
picked up during the immunoscreening and sequencing of several independent
clones from the same library as well as exclusion of polymorphisms is mandatory.
2.5.4
Viral Genes
A virus-encoded antigen that elicits an autologous antibody response is the env protein
of the human endogenous retrovirus HERV-K10, which was found in a renal
cell cancer and in a seminoma.
2.5.5
Antigens Encoded by Over-expressed Genes
Over-expressed genes code for many tumor antigens identified by SEREX, which has
an inherent methodological bias for the detection of abundant transcripts. The members
of this antigen class are expressed at lowlevels in normal tissues (usually detectable
by RT-PCR, but often missed by Northern blot analysis), but are up to 100-fold
overexpressed in tumors. Examples are HOM-RCC-3.1.3, a newcarbonic anhydrase
CA), which is overexpressed in a fraction of renal cell cancers [7], and the Bax inhibitor
protein 1, which is overexpressed in gliomas [21].
2.5.6
Amplified Genes
Amplified genes may also code for tumor antigens. The overexpression of a transcript
resulting from a gene amplification has been demonstrated for the translation
initiation factor eIF-4g in a squamous cell lung cancer [11].
2.5.7
Splice Variants of Known Genes
Splice variants of known genes were also found to be immunogenic in cancer patients.
Examples are NY-COL-38 and restin, which represents a splice variant of the
formerly described cytoplasmic linker protein CLIP-170 [23].
2.5.8
Cancer-Related Autoantigens
Cancer-related autoantigens are expressed ubiquitously and at a similar level in
healthy as well as malignant tissues. The encoding genes are not altered in tumor
samples. However, they elicit antibody responses only in cancer patients, but not in
healthy individuals. This might result from tumor-associated post-translational modifications
or changes in the antigen processing and/or presentation in tumor cells.
An example is HOM-MEL-2.4, which represents the CCAAT enhancer binding protein.