We’ve heard about many different cytokines
and it is very clear that they are crucially
important in playing many, many different
roles in controlling immune responses.
But they are potentially very dangerous molecules
if they are produced in excessive quantities.
And this can happen in pathological situations where the
cytokines are produced inappropriately and can cause pathology.
There is therefore a need to develop therapeutic
agents that can block the activity of cytokines.
And one way of doing that is to
produce monoclonal antibodies.
These antibodies could be directed against the
cytokine themselves, or alternatively, they could
be directed against cytokine receptors, and
prevent binding of the cytokine to the receptor.
Of course such antibodies
should not trigger the receptor.
So we need to make sure that such antibodies don’t mimic
the effect of cytokine in triggering the receptor.
But one can produce such antibodies
that essentially get in the way of the
cytokine binding to the receptor, but
do not themselves trigger the receptor.
And here’s an example of a number of agents
that are used therapeutically in the clinic.
Some of these are antibodies against cytokines,
others are antibodies against cytokine receptors.
I won’t read through this, you can
read it perfectly well yourself.
I’ll just pick out one
of these as an example.
If you look in the middle
there you can see anti-TNFα.
And this is an agent that is used actually in a number
of different conditions - rheumatoid arthritis, plaque
psoriasis, Crohn disease, ulcerative colitis, ankylosing
spondylitis, and so forth.
In all of these conditions, there is excessive
production of TNFα that is contributing to the pathology.
So these agents, at least in a subset of patients in each
of these groups, can be very beneficial in treatment.
Conversely, sometimes in a pathological
situation, there may be either underproduction
of a cytokine or it may be that one can
beneficially stimulate responses using cytokines.
So as well as the situation where you may want
to block cytokine activity, there are other
pathological situations and disease situations
where you can use cytokines as therapeutic agents.
And again, I’m not going to
read through this whole list.
But interferons clearly have anti-viral activity,
so can be of potential use in infection.
Interleukin-2 is an immunostimulatory cytokine, so you
can use that to stimulate immune responses and so forth.