Biomedical Engineering Reference
In-Depth Information
13.3.8 Additional therapeutic applications of monoclonal antibodies
Thus far, the discussion relating to the medical uses of monoclonals has focused exclusively
upon cancer. Monoclonal antibodies (and their derivatives), however, have a far broader potential
therapeutic application. Actual/potential additional uses include detection and treatment of cardio-
vascular disease, infectious agents, and various additional medical conditions (Table 13.2).
Various antibody preparations have been developed that facilitate imaging of vascular-related
conditions, including myocardial infarction, deep vein thrombosis and atherosclerosis. Anti-my-
osin monoclonal antibody fragments (Fab) labelled with
111
In, for example, have been used for
imaging purposes in conjunction with a planar gamma camera. The antibody displays specifi city
for intracellular cardiac myosin, which is exposed only upon death of heart muscle tissue induced
by a myocardial infarction (heart attack).
Imaging monoclonals could be of use in visualizing the sites/extent of focused bacterial infec-
tions. This could be achieved by using radiolabelled antibodies displaying binding affi nity for
specifi c bacterial surface antigens. A related, but indirect, approach may entail use of imaging
antibodies capable of detecting granulocytes and various other leukocytes that congregate at the
sites of infection.
It has been estimated that 1-2 per cent of the US population suffer from autoimmune con-
ditions, including rheumatoid arthritis, MS and some forms of diabetes. In many instances, an
autoimmune response results from the inappropriate activation of a specifi c subset of B- and/or
T-lymphocytes. The most common immunotherapeutic approach to potentially treat such diseases
is to induce depletion of the individual's T- and B-cell populations. This could be achieved by ad-
ministration of an antibody raised against a surface antigen present on such cells. Initial trials, for
example, have shown that injection of an (unconjugated) anti-CD4 antibody (cell surface glyco-
protein present on many T-lymphocytes) over 7 days signifi cantly reduced the clinical symptoms
of rheumatoid arthritis for several months.
Antibodies have and likely will fi nd additional use in transplantation-related medicine. In gen-
eral, cell-mediated immunological mechanisms are responsible for mediating rejection of trans-
planted organs. In many instances, transplant patients must be maintained on immunosuppressive
drugs (e.g. some steroids and, often, the fungal metabolite cyclosporine). However, complications
may arise if a rejection episode is encountered that proves unresponsive to standard immuno-
suppressive therapy. Orthoclone OKT-3 was the fi rst monoclonal antibody-based product to fi nd
application in this regard.
This antibody is raised against the protein-based CD3 antigen, present on the cell surface of
most T-lymphocytes. I.v. administration of (unconjugated) antibody appears to block normal func-
tioning of such T-cells and promote their clearance from the blood. However, upon cessation of
antibody administration, CD3 positive cell numbers rapidly revert to normal values. Therefore,
maintenance immunosuppressives (e.g. with cyclosporine) must subsequently be restored.
A number of additional antibody-based products aimed at preventing transplant rejection have
now gained general marketing authorization. Simulect (chimaeric antibody) and Zenapax (human-
ized antibody) were approved in the late 1990s (Table 13.2). Their engineered nature has greatly
reduced the HAMA response upon their administration to humans. Both products target the IL-2
receptor and, hence, bind fairly selectively to activated immune system cells, especially activated
T-lymphocytes, monocytes and macrophages. Binding prevents further cellular proliferation and,
hence, dampens the immune system's attempts to destroy the transplanted tissue.
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