During my pathology course last year, monoclonal antibodies were one of those things I just couldn't 'get'. It was explained to me numerous times, by increasingly more irate and disappointed looking supervisors, but every time it was re-mentioned in lectures and supervisions I would sort of stare despairingly at whatever piece of paper was in front of me thinking 'what the hell are they again'.
"Something to do with mice, and antibodies, and making them human, or something" was usually the best I could do.
So when the subject appeared yet again during this years course, I decided to finally look it up properly and work out just what was going on.
Antibodies look like this:
The two variable regions recognise bind to antigen (parts of invading bacteria) leading to the invading bacteria being destroyed. Antibodies produced in the body are polyclonal, because each one has a different variable region and can target a different antigen (until a threat is realised in which case they massively overproduce the relavent antibody).
The idea of monoclonal antibody therapy is to produce a large number of essentially the same antibody, that can find and potentially destroy a specific target. The idea was to produce a kind of 'magic bullet' that went through the body picking out the specifically ill parts and removing them. And antibodies are very specific, and can be targeted to lots of different proteins.
The problem with producing them is that a single B cell (antibody-producing cell) will only last a few generations before dying. Not long enough to produce the large amounts of specifically-target antibody needed for therapy. The original solution to this problem was to use a technique known as hybridoma. Individual B cells that had been grown in mice and produced antibodies that destroyed whatever target the therapy was being designed to remove were fused with immortal myeloma cell lines. The B cell could then propagate for much longer, secreting monoclonal antibodies. The main problems with this technique were that is was slow and laborious and created problems for purifying the antigen.
The most modern technique I know of (although others are being developed) is called SLAM, which stands for Selected Lymphocyte Antibody Method. B cells are isolated from mice (or rabbits, other animals can potentially be used as well) and grown in little plastic wells until they start secreting antibodies. Single B cells are then isolated, and screened for activity. The relevant antibody genes are then cloned through PCR and expressed as recombinant antibodies. This technique is a lot faster and produces high affinity antibodies from a number of species.
Monoclonal antibodies are used in various drugs currently on the market. Lymphomas (cancerous B cells) can be treated with Zevalin (R) or Bexxar (R). Apparently on 3 February 2005, the New England Journal of Medicine reported that 59% of patients with a B-cell lymphoma were disease-free 5 years after a single treatment with Bexxar.
The thing is though, I'm being taught this as a biochemist student/researcher, not as a medical researcher. Which means that I have very little idea how useful, common, or applicable most of these techniques and products are. Academic researchers and medical researchers seem to live a world apart, something that hit me particularly hard during the conference. You could almost always tell, about half way through a talk, whether the speaker was a medical or academic researcher. There doesn't seem to be a whole lot of cross-talk between them either, which is a pity because academic research does often come up with the odd useful medical application, but of course they aren't in any position to implement it.
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