Biomedical Frontiers: Spring 1994, Vol.1, No.3
Special Technology Transfer Issue
Bernard Erlanger: Makes Antibodies Mimic Bioactive Small Molecules

When Dr. Bernard F. Erlanger first made antibodies to steroids in the 1960s a major pharmaceutical company expressed interest in the antibodies' contraceptive potential. At the company's request, he went to the dean of Columbia's medical school for permission to patent the antibodies. But he was told patenting research findings made in a medical school was unethical.

Times have changed. Now Dr. Erlanger, professor of microbiology, and the University hold several patents on processes and molecules related to antibodies both to receptors and to their ligands. He and his laboratory have had particular success in creating antibodies that mimic drugs, such as taxol, and imitate bioactive receptor ligands such as adenosine, acetylcholine, thyroid stimulating hormone, and aldosterone.

To isolate these impersonator antibodies, Dr. Erlanger exploits a one-step auto-anti-idiotypic strategy. This approach takes advantage of the fact that during immunization of an animal with a substance such as a small organic molecule, antibodies to the substance (Ab1) as well as antibodies to the antibodies (Ab2) will be made. Some of the Ab2 antibodies, called auto-anti-idiotypic antibodies, although proteinaceous immunoglobulins, have biological activities similar to the low molecular weight substance used in the original immunization.

In fact, Dr. Erlanger recently isolated an anti-idiotypic antibody so like the anti-cancer agent taxol that in test tube experiments it, like taxol, assembled microtubules from their component tubulin subunits--the first example of an antibody assembling a supramolecular structure from soluble cellular components. Taxol works as an anti-cancer agent by stabilizing microtubules in cancer cells so the cells cannot divide.

His laboratory has sequenced the binding site of the taxol-aping antibody because clarifying its amino acid structure could lead to new taxol-like anti-cancer drugs and to a better understanding of how taxol binds to microtubules and inhibits multiplication of tumor cells. Dr. Erlanger also has prepared monoclonal antibodies against taxol that currently are used to monitor taxol levels in patients under treatment and to identify other taxol-like substances in plant extracts.