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

2.5.9
Non-Cancer-Related Autoantigens
Non-cancer-related autoantigens are expressed in most human tissues; in contrast to
cancer-related autoantigens, antibodies against these antigens are found in non-tumor
bearing controls at a similar frequency as in tumor patients. An example is
HOM-RCC-10 which represents mitochondrial DNA and HOM-TES-11 which is
identical to pericentriol material (PCM-1).
2.5.10
Products of Underexpressed Genes
2.6 Incidence of Antibodies to SEREX Antigens and Clinical Significance
An antigen was detected during the SEREX analysis of a hepatocellular carcinoma,
which was underexpressed in the malignant tissue when compared to normal liver [24].
2.6
Incidence of Antibodies to SEREX Antigens and Clinical Significance
The analysis of sera from patients with various malignant diseases and from healthy
controls showed that different patterns of serological responses against SEREX antigens
exist. Clinically most interesting is the group of antibodies that occurs exclusively
in patients with cancer. Such strictly tumor-associated antibody responses are detected
with varying frequencies only in the sera of patients with tumors that express the respective
antigen. Examples are antibodies against HOM-TES-14/SCP-1 [10], NY-ESO-I
[9] and against several antigens cloned from colon cancer [22]. The incidence of tumorassociated
antibodies in unselected tumor patients ranges between 5 and 50% depending
on the tumor type and the respective antigen. The antibodies against many
SEREX antigens are only detected in the patient whose serum was used for the SEREX
assay. A third group of antibodies occurs in cancer patients and healthy controls at a similar
rate. While most of these antibodies are directed against non-cancer-associated,
widely expressed autoantigens, e.g. poly-adenosyl-ribosyl transferase, antibodies of
this category are also found to be directed against antigens with a very restricted expression
pattern, e.g. restin. Restin represents a differentiation antigen, since its expression
is limited to Hodgkin and Reed-Sternberg cells and immature dendritic cells.
There is little information on the clinical significance of antibody responses and
their correlation with the clinical course of the malignant disease. Well-designed prospective
studies are necessary to answer the question, whether and which antibodies
are (alone or in combination with others) valuable for the diagnosis and/or the evaluation
of the response to therapy of malignant diseases. Why only a minority of the
patients with an antigen-positive tumor develop antibodies to the respective antigen,
remains enigmatic. From anecdotal observations we have the impression that antibodies
are only found in a patient's serum, if the tumor expresses the respective antigen.
Antibody titers drop and often disappear when the tumor is removed or the patient
is in remission.
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