It’s drug targeting week (in my world anyway)

Today I met a pretty awe­some person (who looks uncan­nily like my uncle). Pro­fessor of phar­ma­ceu­tical sci­ences Ban-​​An Khaw is an immunology guy, or at least that’s how he clas­si­fied him­self when I asked for his back­ground story. And what an inter­esting story it is!

A few decades ago, Khaw fig­ured out a way to diag­nose var­ious forms of heart cell damage — the damage could be from heart attack, a car­diac autoim­mune defect, a heart trans­plant rejec­tion, it didn’t matter. If the cells were dam­aged, Khaw could find them.

When a heart cell gets hurt, the outer mem­brane rup­tures, exposing the con­trac­tile units of the cells just beneath it. Khaw fig­ured that if he tagged imaging mol­e­cules (which glow at dam­aged sites) to anti­bodies that seek out those con­trac­tile mechi­nary in the muscle cells, then he could find places where they were exposed and by exten­sion, places where the heart tissue has been damaged.

He got pretty far with this work pro­gressing to the point of drug devel­op­ment and FDA approval, but due to var­ious unre­lated cir­cum­stances, the com­pany he was working with put the project on hold. In the mean­time, car­di­ology moved in a dif­ferent direc­tion, he said.

And so did Khaw. He real­ized that his tag­ging approach could be useful in other ways, in par­tic­ular for a more effi­cient, less inva­sive cancer diagnosis.

The cur­rent tech­nology allows doc­tors to see tumors when they have mass of greater than 1 or 2 grams. “But you want to be able to see mil­ligram amounts,” said Khaw. “You want to see it before it’s large enough so it can send out metastatic lesions.” And this is exactly what he accomplished.

One of Khaw’s method can detect a single can­cerous cell in just a few mil­li­liters of blood.

Next he thought that instead of tag­ging imaging mol­e­cules, he could actu­ally tag drug mol­e­cules, such that drugs could be deliv­ered directly to a can­cerous cell, bypassing the healthy ones and thus avoiding many of the toxic effects that chemotherapy is typ­i­cally asso­ci­ated with.

This is sim­ilar to the work I told you about yes­terday, but instead of car­rying the drug inside a pouch, Khaw attaches the small drug mol­e­cules to a polymer and send the prover­bial “truck load of grenades” to the cancer cells that have been tagged with an anti­body com­plex (or other kind of tag). The tag rec­og­nizes the cancer cells, but not healthy ones. When the truck full of grenades docks on a cancer cell, the cell pulls it inside. Once in there, the nat­ural diges­tion processes break the com­plex down, dis­as­so­ci­ating the drug from the polymer.

This is impor­tant: When the polymer and drug are attached, the drug is inac­tive. But once it detaches it becomes toxic. So, it only becomes toxic when it’s inside a cell, which will only ever be a cancer cell. Get it?
There is a lot more to say about this work, but I’m going to save it for future stories…to keep you on the edges of your seats. Stay tuned, a few new arti­cles have recently come out of Khaw’s lab, which I think you’ll find rather interesting!