Camel Antibodies Guide Therapies To Tumors

We've learned a lot about destroying cancers in recent decades, but a huge problem remains: How do we target treatments so they destroy tumors while leaving healthy cells intact?

All animals have antibodies to destroy threats, be they bacterial, viral or cancerous. The idea of attaching to an antibody something with the firepower to destroy cancer cells seemed a perfect fit, but has proven very hard. An ideal destroyer would be a virus that replicates inside cancer cells, killing them before infecting others.

"For decades, investigators have been putting human or mouse antibodies on viruses, and they haven't worked—the antibodies would lose their targeting ability," says Dr. David Curiel of Washington University in St. Louis. "It was a technical problem. During replication, the virus is made in one part of the cell, and the antibody is made in another. To incorporate the two, the antibody is dragged through the internal fluid of the cell. This is a harsh environment for the antibodies, so they unfold and lose their targeting ability."

However, camels, alpacas and other camelids have smaller and more stable antibodies than those of other mammals. Curiel thought these antibodies might survive the trip through the hostile desert of cancer cell interiors.

In Molecular Therapy – Oncolytics, Curiel announces the success of the first stage in his quest to turn this idea into a viable cancer treatment. "We found that when we incorporated the camelid antibodies into the virus, they retained their binding specificity," Curiel said. "This opens the door to targeting these antibodies to specific tumor markers."

So far, the technique has only been demonstrated in human cells grown in culture, but Curiel hopes to move on to research in vivo.

How camelids (and sharks) came to have this class of smaller antibodies, while other species missed out, is unknown. However, scientists do understand how they differ. Antibodies are generally Y-shaped, with the tips of the arms shaped so they lock onto the invasive bodies they have evolved to destroy. Such a shape works well, but also unfolds while passing through an inhospitable wasteland like that within cells. The camelid antibodies attach directly to the stem.

^{Credit: Anypodetos via wikimedia commons. Shark (left) and camelid (center) antibodies compared with those of other animals. Roughly half of camelid antibodies also resemble those on the right.}

Viruses are used against cancer cells already. However, these operate not by targeting the cells, but by entering a variety of cells and only replicating within tumors. That stops the virus killing all the cells in the body, but it is also highly inefficient since most copies of the virus go somewhere where they can't do their job. Curiel says, "These viruses are already engineered to replicate only in tumors. These camelid antibodies would enable them to become even more tumor-specific and open the door for use in metastatic cancer."