Sì, questa sperimentazione compassionevole è stata fatta moltissimi anni fa. C'è comunque un trial clinico in atto, i cui risultati dovrebbero arrivare entro l'anno (vedi http://clinicaltrial.gov/ct2/show/NCT01 ... lin&rank=1).uffa2 ha scritto:questo vuol dire sperimentazione in vivo su dei malati, insomma, niente vetrini, ma real life... bene, bene, se non è una boiata quel che ho letto è un passo grandioso perché vuol dire un salto bello lungo nel time to market...Dora ha scritto:Dr. Trauger will also present a short summary of the clinical experience from a previous compassionate use study in HIV-infected subjects[/b]. (...)
Sto leggendo una interessante intervista fatta lo scorso ottobre a Eric Rosenberg, l'infettivologo del Massachusetts General Hospital che sta dirigendo il trial. Ne riporto qualche passaggio, perché mi pare che dia indicazioni utili a capire meglio questo mAB e in generale gli anticorpi monoclonali, di cui fino ad oggi ci siamo occupati abbastanza poco, ma che stanno diventando sempre più importanti in un numero sempre maggiore di patologie.
Cytolin - a monoclonal antibody therapy for HIV?
D: So Cytolin, it may be useful for HIV and it is a monoclonal antibody. What is a monoclonal antibody?
R: First we should look at what is an antibody. An antibody is a molecule made by B cells, a type of white blood cell in the body and an antibody has a very high specificity for a given molecule. Antibodies are one reaction the immune system has to discovering a foreign body whether it’s somebody else’s skin in a transplant or a germ that doesn’t really belong in the body. Antibodies are things the body makes that stick to these foreign bodies and often they help the body get rid of them in different ways.
D: What category of medicine do monoclonal antibodies fall under?
R: They are unique: they are antibodies that are all the same made by identical immune cells cloned from an original. This is good because you can count on them to behave in more or less predictable ways. They are, like vaccines, an immune based therapeutic when used as medicine.
D: Why are these antibodies called ‘mono’ instead of just ‘an antibody’?
R: Because each antibody has a given specificity, similar to how every key fits into a very specific type of a lock in a door. Antibodies are the same way, your body makes billions of different types of antibodies and each antibody recognizes a very specific type of target. The body makes lots of different kinds of antibodies; a monoclonal antibody is just basically an antibody with one clonal type. So it is an antibody produced in great quantity that only recognizes a very specific thing.
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D: What is the work you are doing with Cytolin?
R: Let’s start with what were some of the early observations in people in which Cytolin was originally used. Some people were given this antibody on a compassionate use basis that resulted in the interesting observation that in some individuals, viral loads dropped and CD4 counts went up. None of these were randomized controlled trials, but we are left with the observation, at least to the physicians administering the medicine, that this monoclonal antibody when given to HIV infected individuals who are out of standard therapeutic options seemed have some benefit. Unfortunately, these stories were mostly anecdotal and therefore it is impossible to know for sure if Cytolin does anything beneficial.. So that was really the basis for wanting to understand in much greater detail if this is a legitimate observation because if so it could be a legitimate therapy, and also what is the mechanism of action? How do you explain what this antibody is doing in the body that would result in HIV viral load dropping and CD4 counts rising?
D: Well to that affect, you spent a little bit of time looking at this antibody in the lab already and you are continuing to work with it so what might you be at liberty to share so far as to what is of interest to you and what you are learning?
R: I think that we are very early in our studies and so we are really not at liberty to say much because we need to do more work, but what I can say is that we have found one or two interesting observations that, if they pan out, may help explain the affect that this antibody is having or how the antibody is actually working.
D: If you look just at the field of HIV right now there are a large number of approved antiretrovirals in different classes already. In what way would a biologic like Cytolin, be of use?
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R: We are not going to know for sure until we understand this antibody better and it goes through clinical trials to see how effective it may be in humans, but I could imagine or I could hypothesize that there are several situations where it may be useful. One situation is relatively early in the course of infection when prior to somebody meeting the traditional criteria for starting antiviral therapy. Perhaps if you gave a monoclonal antibody like this to somebody before they meet the need for starting antiviral therapy, if you can get a drop in viral load and a rise in CD4 count you may prolong the time in which they can actually stay off of standard HIV therapy. So one theoretical use would be to give it early in disease to buy somebody more time off of traditional HIV medicines.
The other potential or theoretical use would be at the other end of the spectrum in those individuals who had run out of other therapy options. Somebody who has got highly drug resistant virus and is not able to bring the viral load down or the CD4 count up using traditional antiretroviral medicines, perhaps giving an antibody like this may buy somebody time or may help to control infection for a longer period of time because they don’t have other drugs that are necessarily effective. That situation would be known as a salvage therapy, where you have run out of your standard options and you are using this to achieve a similar effect.
D: Is there any a priori reason to think or believe that using an antibody of this type if it were to work, as an additional component to a cocktail of some kind, would be beneficial?
R: I could imagine situations where using an antibody in the presence of antiviral drugs could be synergistic. That is there could be an added beneficial effect. But it really all will come down to how this antibody works, and so in order to understand what the effect is going to be of the antibody we first need to determine how it works, and until we do that it is impossible to predict whether there would be any sort of additive or beneficial effect.
D: Is it equally unknown whether or not the virus will grow resistant to Cytolin like it does to most of the drugs that I have read about and looked at over the years? Is there any reason a priori to think that the virus could get resistant to this antibody? Or is there anything about antibodies that makes them fundamentally different than the drugs that are being used to treat HIV right now?
R: If the antibody is working by binding to a specific part of the virus, we know that there is a high likelihood that the virus may mutate and change and escape from the ability of the antibody to bind. However, there is a good chance that if this particular monoclonal antibody works, that it is working through a more indirect mechanism, where it is not actually binding to virus itself but it may be binding to a cell and telling the cell to do something that may have an antiviral effect.
D: If that happened would that make it less likely that the virus could figure a way around that?
R: Yes, because the virus would not be binding to a cell so if the virus mutates it doesn’t really matter because this antibody may not be directly interacting with the virus.
D: Did studying this so far teach you anything new about HIV, as opposed to the antibody?
R: It may, and I say it may because it really depends on the next phase of our studies if we could take some of our observations a little bit further not only will we gain insight into how this antibody is working but we may also be able to learn other different strategies that the body may employ to fight viruses.
D: The antibody is being humanized. Can you explain a little bit for a lay audience what does that mean and why is it relevant? (Ed. The antibody has been successfully humanized recently). [vedere http://www.hivforum.info/forum/viewtopi ... 2332#p2332]
R: Antibodies are not something typically made in a laboratory, usually antibodies are grown from another living thing. The first generation was actually made from mice, so it is a murine or mouse based monoclonal antibody and the next generations of antibodies that are being developed are “humanized” to look and possibly behave more like an antibody antibody made by a human instead of a mouse. In the case of Cytolin, they are actually putting human sequences into the mouse cell, which is a way to humanize the murine version.
D: We already know it has been used in people, but are there likely to be clinical trials with this?
R: I would guess that when we figure out in a convincing way the mechanism of action of this antibody and if it seems, based on what we learn, plausible and likely that administering this antibody would have a beneficial effect then I would image that the next step in development would be to do studies in humans.