Cell-mediated Immunity: Therapeutic Blocking of Pathological Cytokines and Therapeutic Cytokines

00:01 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.

00:11 But they are potentially very dangerous molecules if they are produced in excessive quantities.

00:17 And this can happen in pathological situations where the cytokines are produced inappropriately and can cause pathology.

00:26 There is therefore a need to develop therapeutic agents that can block the activity of cytokines.

00:34 And one way of doing that is to produce monoclonal antibodies.

00:39 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.

00:52 Of course such antibodies should not trigger the receptor.

00:56 So we need to make sure that such antibodies don’t mimic the effect of cytokine in triggering the receptor.

01:02 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.

01:12 And here’s an example of a number of agents that are used therapeutically in the clinic.

01:19 Some of these are antibodies against cytokines, others are antibodies against cytokine receptors.

01:26 I won’t read through this, you can read it perfectly well yourself.

01:29 I’ll just pick out one of these as an example.

01:32 If you look in the middle there you can see anti-TNFα.

01:35 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.

01:49 In all of these conditions, there is excessive production of TNFα that is contributing to the pathology.

01:56 So these agents, at least in a subset of patients in each of these groups, can be very beneficial in treatment.

02:08 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.

02:21 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.

02:35 And again, I’m not going to read through this whole list.

02:38 But interferons clearly have anti-viral activity, so can be of potential use in infection.

02:47 Interleukin-2 is an immunostimulatory cytokine, so you can use that to stimulate immune responses and so forth.