T-cell immunotherapy is one of most promising tools in cancer therapy. Different preclinical and
clinical studies have demonstrated the ability of T lymphocytes to control tumor growth. Because
tumor-specific CTLs are responsible for the lysis of tumor cells, many research groups have channeled
their efforts to the induction of CTL responses and to the identification of T-cytotoxic cell determinant
peptides from human tumor antigens.
These TCds are presented at the surface of tumor cells in the form of a complex TCd-MHC-I, which
is recognized by the T-cell receptor of CTL. However, despite the well-established role of CD4 T cells
to induce immune responses, and in particular antitumor responses (16–20), much less effort has been
put to identify T-helper determinants (THds) from tumor antigens.
2. Carcinoembryonic antigen
Carcinoembryonic antigen was first discovered in 1965 by Gold and Freeman. It is a glycoprotein that
is a member of a large gene family that consists of 29 genes divided into three subgroups that include
the CEA-like glycoproteins and the pregnancy-specific glycoproteins (PSGs).
All these proteins are members of the much larger immunoglobulin supergene family. CEA is also
known as CD66 or CEACAM5 and the nomenclature for the entire CEA and PSG families can be
found in Beauchemin et al. CEA has a molecular mass of 180–200 kD depending on the extent of its
glycosylation. The protein consists of a series of immunoglobulin-like domains, at the N-terminus is
108 amino acid v-domain followed by three pairs of c2-like domains each of 178 amino acids. Each c2
loop domain is held in conformation by a single disulphide bond.
There is a small hydrophobic C-terminal domain (26 amino acids) that is modified to give a GPI-linked
membrane anchor. This anchor can be cleaved by phospho-inositol specific phospholipases C and D to
release CEA in a soluble form. The structural features of the protein also allow up to 28 tetra-antennary
complex carbohydrate chains of the N-linked type.
The complete gene for CEA has been cloned and includes a promoter region that appears to confer
organ and cell type-specific expression. Since its discovery in 1965 a very large number of studies have
been carried out to determine the effectiveness of CEA as a clinically useful tumor marker. Serum
elevations of CEA are seen in about 60% of presenting colorectal cancer patients.
While not considered useful as a cancer screen for the general population due to high false positive and
false negative rates, CEA is used to monitor tumor recurrence following surgery and as a marker for
A small rise in CEA can be predictive of recurrence following curative surgery for colorectal cancer
and can result in detection of recurrence up to a year before the onset of clinical symptoms. A recent
study has even suggested that elevated serum CEA levels in people over 50 are predictive of increased
CEA mRNA expression has recently been shown to be useful as an early marker for recurrence in
pancreatic cancer. Other members of the CEA gene family (e.g. CEACAM6 or NCA-90) can also be
used for prognosis and as predictors of tumor recurrence.
CEA is widely used as a target antigen for radio-immunodetection of occult metastasis and for radio-
immunotherapy in patients with CEA producing cancers. More recently it has been used as a preferred
antigen for the development of anti-colorectal cancer vaccines.
Elevated serum CEA levels are associated with liver metastasis and are used as a prognostic indicator
. In the normal colon CEA is produced by mature colonocytes and is localized to the apical