Biomedical Engineering Reference
In-Depth Information
sarcoma virus, avian myelocytomatosis virus, and various murine leukaemia viruses. Thus far,
the only well-characterized human RNA transforming virus is that of human T-cell lymphotropic
virus-1 (HTLV-1), which can induce adult T-cell leukaemia/lymphoma. The identifi cation of
antigens uniquely associated with various tumour types and the identifi cation of additional can-
cer-causing viruses remain areas of very active research.
Another group of antigens associated with some tumour types are oncofoetal antigens. These
antigens are proteins that are normally expressed during certain stages of foetal development.
Subsequent repression of their structural genes, however, prevents their expression at later stages
of development and/or into adulthood. Characteristic of some cancers is the re-expression of onco-
foetal antigens. Some such antigens remain attached to the cancer cell surface, whereas others are
secreted in soluble form. Although these oncofoetal proteins are not recognized as foreign by the
host's own immune system, they do represent important potential diagnostic markers. Although
some such markers have been identifi ed, efforts continue to identify additional members of this
family.
CEA and
-fetoprotein (AFP) represent the most extensively characterized oncofoetal antigens
thus far. We have already encountered CEA in the guise of its use as a marker for cancers of the co-
lon and rectum. CEA is a 180 kDa integral membrane glycoprotein. It also may be secreted into the
blood in soluble form. It is expressed mainly in the gut, liver and pancreas, during the fi rst 6 months
of foetal development. However, it is now known to be expressed (although at greatly reduced
levels) by adult colonic mucosal cells and in the lactating breast. Elevated levels of either soluble
(serum) or cell-bound CEA are normally indicative of cancers of the gastrointestinal tract.
AFP is a 70 kDa glycoprotein found in the circulatory system of the developing foetus. It is
synthesized primarily by the yolk sac and (foetal) liver. AFP is present only in vanishing low
quantities in the serum of adults (where it is replaced by serum albumin). Elevated adult serum
levels of this marker are often associated with various cancers of the liver, as well as germ cell
tumours. It is also sometimes expressed by gastric and pancreatic cancer cells. Although a useful
tumour marker, increased serum AFP levels also often accompany cirrhosis and some other non-
cancerous liver diseases.
CA125 represents an oncofoetal protein that is expressed by up to 90 per cent of ovarian adeno-
carcinomas. Some of the protein is released from the tumour site into the general circulation. El-
evated serum CA125 levels, therefore, have some diagnostic value. Imaging of actual tumour sites
can also be undertaken using radiolabelled antibody coupled to immunoscintigraphy. Indimacis-
125 is the trade name given to such a product approved in 1996 for use in the EU. The product is
an
111
In-labelled F(ab)
2
fragment derived from a murine hybridoma cell line. Although some of the
product is likely absorbed by the circulatory form of the oncofoetal protein, the product has proven
effective in imaging relapsing ovarian adenocarcinoma.
In summary, TSA-based complications in the context of developing antibody-based cancer
therapies include:
α
•
Limited numbers of TSAs currently characterized.
•
Some cancer types, depending upon their cause, may display unique TSAs in different patients.
•
TSAs are often expressed, albeit at lower levels, by one or more additional (non-transformed)
body cell types.
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