Recently BioPharm International was fortunate to catch up with editorial advisory board member K. John Morrow to hear his reflections and observations about
current trends in antibody therapy research. Dr. Morrow, director of biological sciences research at Meridian Biosciences,
spoke enthusiastically about what biotechnology researchers hope to accomplish in the near future.
K. John Morrow, Jr., Ph.D.
What are some of the key methods used in antibody research?
John Morrow: One area that's encouraging is the study of libraries or genetic databases (for genomes) looking for unique gene sequences
to develop better diagnostic tools for infectious disease. A current approach is to use either genomics or proteomics, going
after markers using antibodies or PCR technology to identify the sequences.
For example, say you're dealing with maybe ten or twenty different bacterial strains that are co-existing in the gut and one
of these is a pathogen, and it's the one you want to get a diagnostic test for, but they're all quite similar. They all have
fairly similar properties; maybe they're members of the same genus. So you look for unique gene sequences and you make peptides
from these gene sequences that are specific to your target organism. Then you can make antibodies to those peptides and screen
the antibodies to see if they uniquely identify your organism.
Isn't this technique used in cancer research?
JM: All cancer genes are present in all the cells of the body, but they may be over-expressed in a cancer cell. You can look for
them by screening the genomes and looking for unique sequences. You look for those, and then once again you make a peptide
from one of the gene sequences — not the whole gene — so you don't have to produce the whole protein, but you just get a particular
peptide that respresents a good target. In many cancer cells, [certain] receptors that are over-expressed. So what you do
is identify the ligand for that receptor, then make a peptide from part of that ligand that will fit into the receptor and
target the cancer cell.
What other areas of study are getting more attention these days?
JM: Another approach that I've been following over the years, is cancer therapy with antibodies. Initially, all the antibodies
that received FDA approval were "naked antibodies." The investigators didn't couple the antibody to a toxin because they tried
that and it didn't work very well. Another approach, the use of antibody fragments, rather than whole antibody molecules,
never worked very well because they're cleared out of the body so fast. But scientists are looking at ways of stabilizing
these antibody fragments and hooking the fragments to toxin molecules and other agents that could target the cancer cell so
you don't have to simply rely upon the host resources.
At this time, numerous companies have FDA approval on antibodies, so they're doing lots of antibody therapies. But to my knowledge,
you don't get cures with these antibodies, you get some remission of the cancer and patients can live longer. But you're not
getting complete, permanent remission.
I think the idea of using various kinds of toxins is coming back now, and it has a bit more credibility than it did originally.
Also, the companies that have all these antibodies produced maybe a hundred different antibodies before they picked the one
that they use in their therapy. So they've got a whole stable full of antibodies that didn't work therapeutically, as naked
antibodies that they can now conjugate to various kinds of toxins, stabilize the sequences, to make them more robust and get
them to really perform well. In the next few years, that area that will really take off.