Monograph: |
Monoclonal antibodies purified :
In recent years considerable interest has focused on
immunological approaches to the treatment of ma-
lignant disease and a number of monoclonal anti-
bodies such as muromonab-CD3 have been or are
being, developed. The use of biological response
modifiers such as interleukins continues to be the
subject of investigation and attempts to develop vac-
cines against individual neoplasms also continue.
Anti-CD4 Monoclonal Antibodies: CD4mAb: Monoclonal
CD4 Antibodies.
Monoclonal antibodies raised against CD4 receptors are un-
der investigation in the treatment of immunologically mediat-
ed disorders, such as rheumatoid arthritis, multiple sclerosis,
inflammatory bowel disease, and various skin disorders, with
the aim of decreasing and eliminating circulating helper T
lymphocytes. One such antibody, keliximab. has also been in-
vestigated in asthma.
Endotoxin Antibodies
Antibodies against the endotoxin of Gram-negative bacteria
have been tried as adjunctive therapy for the treatment and
prevention of Gram-negative bacteraemia and shock.
Early preparations consisted of antisera prepared from the
sera of donors immunised with Escherichia coli j5, these
were superseded by human and murine IgM monoclonal an-
tibodies. Nebacumab (HA-IA) is a human monoclonal IgM
antibody that binds specifically to the lipid A domain of en
dotoxin. Lipid A in the circulation releases tumour necrosis
factor and other cytokines from macrophages and endothelial
cells which may ultimately culminate in physiological effects
such as multiple organ failure. Despite early promising results
of clinical studies the safety of nebacumab in patients without
Gram-negative septicaemia has been questioned and the
product has been withdrawn from the European market pend-
ing the results of further studies. A single dose of nebacumab.
100 mg administered by intravenous infusion over 15 to 30
minutes was used.
A murine monoclonal IgM antibody (edobacomab; E5) has
Also undergone clinical trials.
Initial promising results in patients with Gram-negative infec-
tions given antibodies against the endotoxin core glycolipid
of Gram-negative bacteria prompted further investigations
using monoclonal antibodies to these endotoxins in the man-
agement of septicaemia.
Studies concentrated on preparations of either human or
murine IgM monoclonal antibodies to the endotoxin of Gram-
negative organisms. A study of nebacumab in 543 patients
with sepsis showed a reduction in mortality from 49 to 30%
in patients with Gram-negative bacteraemia. However, the
study was severely criticised on the grounds that this group of
patients could only be identified retrospectively, and overall
nebacumab had no effect on mortality. A subsequent study
involving 2199 patients with septic shock was stopped when
the mortality rate in patients without Gram-negative bacterae-
mia was found to be higher in those receiving nebacumab
than in those receiving the placebo. The mortality rate was
unchanged in patients with Gram-negative bacteraemia.
Doubts about the safety and clinical efficacy of nebacumab
were sufficient lo lead to its withdrawal from the European
market although some clinical studies have continued, in-
cluding a study in children. In the meantime, doubts over the
role of endotoxins in the development of the sepsis syndrome
have been raised although there has been a report* of the de-
velopment of full clinical manifestations of septic shock in a
man following self-administration of a single large dose of
endotoxin in an attempt to treat a tumour.
An initial study of the murine monoclonal antibody edoba-
comab showed some benefit in patients with Gram-negative
infections but not in shock, although there was no overall im-
provement in survival at 30 days. A subsequent study of pa-
tients with similar characteristics to those who had responded
in the first study also failed to show an improvement in sur-
vival at 30 days although some beneficial responses were
seen in patients with organ failure.
Edrecolomab
Monodonal Antibody 17-1 A.
Edrecolomab is a monoclonal antibody of murine origin di-
rected at epithelial cell surface glycoproteins that has been
used as adjuvant therapy following surgery in patients witth
colorectal cancer. It is given by intravenous infusion
over 2 hours, in an initial dose of 500 mg, followed by 4 fur
ther doses of 100 mg at monthly intervals. The drug is of
murinewigin and most patients develop antibodies following
administration. Hypersensitivity reactions, including anaphy-
lactic reactions, have occurred.
It has also been tried for other malignant neoplasms including
pancreatic cancer.
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