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

teristics of identified antigens an electronical SEREX database was initiated by the
Ludwig Cancer Research Institutes, which is accessible to the public (www.licr.org/
SEREX.html). By December 2001, more than 2000 entries had been made into the
SEREX database, the majority of them representing independent antigens. The
SEREX database is not only meant as a computational interface for discovery information
management, but also as a tool for mapping the entire panel of gene products
which elicit spontaneous immune responses in the tumor bearing autologous
host, for which the name ªcancer immunomeº has been coined by L. J. Old (LICR,
NewYork Branch). The cancer immunome which is defined by using spontaneously
occurring immune effectors from cancer patients as probes gains increasing interest,
since it has been shown that many antigens may be valuable as new molecular
markers of malignant disease. The value of each of these markers or a combination
of them for diagnostic or prognostic evaluation of cancer patients has to be determined
by studies which correlate the presence or absence of these markers with clinical
data.
The multitude of tumor-specific antigens identified by the SEREX approach demonstrates
that there is ample immune recognition of human tumors by the autologous
host's immune system. Together with the identification of T lymphocyte epitopes a
picture of the immunological profile of cancer is emerging. Knowledge of the cancer
immunome provides a newbasis for understanding tumor biology, and for the development
of newdiagnostic and therapeutic strategies for cancer. The specificities
of the antigens expressed by human tumors and detected by SEREX vary widely,
ranging from tumor-specific antigens to common autoantigens. This surprising
finding together with the observation that some ubiquitously expressed antigens elicit
immune responses only in cancer patients suggest that the context in which a
protein is presented to the immune system (e. g. the context of ªdanger) is more decisive
for its immunogenicity (and breaking of tolerance) than its more or less tumor-restricted
expression. Our results obtained with the SEREX analysis of many
human tumors also showthat, besides the rare tumor-specific antigens, there is a
great majority of widely expressed autoantigens which are presented by the tumor
and recognized by the immune system. The presentation of common autoantigens
by a given tumor (presumably in the context of ªdangerº) induces a broad range of
autoimmunity, and it is only if the tumor happens to express and present tumorspecific
molecules that tumor-specific autoimmunity can occur: specific tumor immunity
is just a small part of broad autoimmunity that is commonly induced by malignant
growth.
2.10
Consequences for Cancer Vaccine Development
2.10 Consequences for Cancer Vaccine Development
The fact that tumors present a majority of molecules that are also expressed in normal
tissue and only a minority of tumor-specific molecules in the context of their
MHC molecules also implies that vaccines using whole tumor cell preparations are
rather unlikely to be successful, because the induction of tumor-specific immunity
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