Worldwide,
tens of thousands of researchers are working feverishly on a cure for cancer,
testing countless new drugs and dozens of novel approaches. Most will end up
in the dustbin. But among the most promising of that small group likely to
make it to market is monoclonal antibody therapy.
That
may sound like a daunting scientific concept to try to wrap one's head
around, but in essence monoclonal antibodies are simple. Most of us are
familiar with antibodies, the road warriors of the human body's immune
system. They're those little Y-shaped proteins that are used to identify and neutralize
foreign objects in the body (like bacteria and viruses) by binding themselves
to the target - called an antigen - and killing it.
Although
one antibody is generally very similar to another in structure, a small
region at the tip of the protein is extremely variable - enough so that there
are millions of distinct antibodies with slightly different tip structures,
or antigen binding sites. This diversity allows the immune system both to
recognize an equally wide variety of antigens and to come up with new
responses to new types of infections.
Now,
what if the body's ability to construct antigen-specific antibodies could be
harnessed in the lab? What if scientists could produce substantial amounts of
a single antibody (whichever one they wanted for a particular antigen) and
that antibody alone, outside of the body? What if our own capacity for
fighting infection could be turned against cancer cells? Wouldn't that be
better than present chemotherapies, which willy-nilly blast diseased and
healthy cells alike?
Of
course it would. Making it happen is another matter.
Fortunately,
many of the technical issues were resolved about 35 years ago, when Cesar
Milstein, Georges Kohler, and Niels Jerne
discovered how to fuse an antibody-producing cell with a cancer cell in the
lab - an effort that won them the 1984 Nobel Prize in Physiology. The
resulting mutant - dubbed a hybridoma - will
produce large amounts of identical antibodies from a unique parent (that's
the "monoclone" part) essentially
forever.
The
remaining challenge was how to put monoclonal antibodies to work against
cancer.
What
researchers came up with was elegant: To borrow from military parlance, they
would create a "smart bomb," an antibody which - when combined with
a cancer-killing drug - would detonate inside the diseased cell.
Though
elementary in conception, the smart bomb was a long time in coming. First, an
antibody had to be developed that would be accepted by the host and would
navigate the bloodstream until it linked to a particular cancer cell. Then
there would have to be a means for a potent cancer drug to be locked to it in
such a way that the bond wouldn't disintegrate along the way; such a failure
would create havoc among healthy cells. Finally, the antibody would have to
be able to release its piggybacked drug once it reached its target.
The
payoff is huge. Not only does this form of therapy allow for much more
precise targeting, it permits the use of cytotoxins
(cancer-killing agents) that are 100 to 1,000 times more potent than traditional
chemotherapy drugs - a toxicity that would cause far too much collateral
damage if they were introduced into the body in a non-specific way.
Fighting
cancer with our own built-in defense mechanisms sounds both logical and at
the same time improbable, since up to now we've had such little luck in
combating the disease ourselves.
Yet
that's the promise of monoclonal antibody therapy, and the good news is that
today it is far down in the research pipeline. Much testing in human subjects
has been done, with results among patients whose cancers were previously
deemed intractable that are nothing short of spectacular.
FDA
clearance has been fast-tracked. The therapy has already been granted
approval at the subcommittee level, with the full agency set to rule by the
end of August. The first monoclonal antibodies with novel linkage systems
binding to potent cytotoxins could hit the market
this year, saving lives and making fortunes for both the company that
developed them and those who invested in it.
Even the most diligent investor can’t keep up
with all the developments in cancer research, let alone build the knowledge
necessary to understand both the promises and challenges they face.
That’s what makes a subscription to Casey
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