Biomedical Engineering Reference
In-Depth Information
The specifi city of antibody-antigen binding should ensure that, once injected into the body, the
antibody will selectively congregate on the surface of only the target cells. Depending upon the
specifi c intended therapeutic/diagnostic application, antibodies employed may have nothing at-
tached to them or may be conjugated to a radioisotope, drug or toxin (Figure 13.3). With the latter
approaches, the antibody is used as a 'magic bullet', delivering a radioactive/drug load to specifi c
cells in the body. All of these various strategies have been adopted in practice, and specifi c exam-
ples will be provided in subsequent sections of this chapter.
In the context of antibody-mediated cell targeting, it is also important to appreciate that bind-
ing of an antibody to a USA can, by itself, trigger a number of responses. In some instances, the
antibody-antigen (Ab-USA) complex is quickly internalized. In other instances, the Ab-USA
complex is shed from the cell surface, whereas in yet other cases binding induces neither response.
The specifi c response triggered is generally only determined by direct experimentation. The induc-
tion of Ab-USA shedding renders an anti-type-specifi c antigen (TSA) antibody clinically useless.
By 2006, a total of 29 such antibody-based products had gained marketing approval in some world
regions at least (Table 13.2). Over half of these aim to detect/treat various cancers, and cancer rep-
resents the single most signifi cant indication for antibody-based products currently in clinical trials.
The application of antibodies in the context of cancer is overviewed in the next section. A minority of
the products approved/in trials are intact antibodies produced by classical hybridoma technology. The
majority are engineered antibodies ('chimaeric' or 'humanized') or antibody fragments. The genera-
tion/rationale for use of such engineered products is also discussed subsequently in this chapter.
13.3.3 Tumour immunology
The transformation of a cell to the cancerous state is normally associated with increased surface
expression of antigens recognized as foreign by the host immune system. These surface antigens,
often termed tumour antigens or tumour surface antigens, are either not expressed at all by the
untransformed cell or are expressed at such low levels that they fail to induce immunological
tolerance.
The presence of tumour-specifi c antigens implies that the immune system should be capable
of recognizing and destroying transformed cells. This concept, known as immunosurveillance,
probably does function to some extent in the body. The immune system does respond to the pres-
ence of some tumours, causing their partial or complete regression. The major anti-tumour im-
mune elements include:
•
T-lymphocytes, which are capable of recognizing and lysing malignant cells.
•
NK cells, which, like some T-cells, can induce lysis of tumour cells. The tumouricidal activity
of NK cells is potentiated by various cytokines (e.g. IL-2 and TNF).
•
Macrophages can destroy tumour cells, largely by releasing damaging lysosomal enzymes and
reactive oxygen metabolites at the tumour cell surface. Macrophages also produce TNF, which
can kill tumour cells by (a) binding to high-affi nity TNF cell surface receptors (which is directly
toxic to the cells) and (b) promoting synthesis of additional cytokines (which can, indirectly,
lead to tumour destruction via activation of other elements of immunity).
Search WWH ::
Custom Search