Biomedical Engineering Reference
In-Depth Information
Immunoglobulins are glycoproteins. The carbohydrate moiety is attached to the heavy chain
(usually the C
H
2 domain) via an N-linked glycosidic bond. Removal of the carbohydrate group
has no effect upon antigen binding, but it does affect various antibody effector functions and
alters its serum half-life.
F
v
V
H
V
H
F
ab
V
L
V
L
C
1
1
H
C
H
C
L
H
H
C
L
2
C
C
2
H
H
F
c
C
3
C
3
H
H
= Carbohydrate
Figure 13.B2
IgG structure
13.3.3.1 Antibody-based strategies for tumour detection/destruction
Clear identifi cation of tumour-associated antigens would facilitate the production of monoclonal
antibodies capable of selectively binding to tumour tissue. Such antibodies could be employed to
detect and/or destroy the tumour cells.
The antibody preparations could be administered unaltered or (more commonly) after their
conjugation to radioisotopes or toxins. Binding of unaltered monoclonal antibodies to a tumour
surface alone should facilitate increased destruction of tumour cells (Figure 13.4). This approach,
however, has yielded disappointing results, as the monoclonal antibody preparations used to date
have been murine in origin. The F
c
region of such mouse antibodies is a very poor activator
of human immune function. Technical advances, allowing the production of human/humanized
monoclonals (see later) may render this therapeutic approach more attractive in the future.
Several clinical trials have evaluated (or continue to evaluate) monoclonal antibodies to
which a radioactive tag has been conjugated. These are usually employed as potential anti-can-
cer agents. The rationale is selective delivery of the radioactivity directly to the tumour site.
Most of the radioisotopes being evaluated are
-emitters. These include istopes of iodine (
125
I,
131
I), rhenium (
186
Re,
188
Re) and yttrium (
90
Y). The medium-energy radioactivity these emit is
capable of penetrating a thickness of several cells. Congregation of radioactivity at the tumour
surface could thus promote irradiation of several layers of tumour cells, as well as nearby
healthy cells. Higher energy
β
-emitters are also being evaluated. Although their effective path
length is only about one cell deep, each emission has a greater likelihood of killing all cells in
its path.
α
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