Antibodies from camelids – a family that includes llamas, alpacas and camels – can withstand the harsh environment inside cells, unlike antibodies from humans and most other animals. This property makes camelid antibodies ideal vehicles for carrying anti-cancer viruses directly into tumor cells, while leaving healthy cells untouched.
This was the conclusion of a study by researchers from the School of Medicine at Washington University in St. Louis (WUSTL), MO, who report their findings in the journal Molecular Therapy – Oncolytics.
Using human cells grown in the lab, senior author David T. Curiel, a distinguished professor of radiation oncology, and colleagues showed it is possible to directly deliver genetically engineered viruses to specific cells.
The idea of engineering a virus so it infects a diseased cell, replicates in it and then bursts the cell, releasing copies to infect other diseased cells, is not new. Many research teams have been working on this type of gene therapy for a long time.
There are therapies in use and being trialed that use anti-cancer viruses. These are not of a type that targets specific tumor cells – they work because the virus is genetically programmed so it only replicates inside a tumor cell.
But to make therapies using viruses that are targeted at specific cell types, you need something like an antibody.
Antibodies are “cop proteins” of the immune system that travel through the bloodstream constantly looking out for potential threats in the form of bacteria, disease viruses or rogue cells.
Most antibodies have a characteristic Y shape, with the tips at the top forming a unique “lock” that only accepts a particular “key” of the specifically hunted pathogen. Once the offending pathogen has been apprehended, then it is handed over to other members of the immune system for destruction.
It is this specific targeting feature of antibodies that makes them attractive vehicles for ferrying viruses to specific cells. But although many studies have been done, they have met with mixed success.
Prof. Curiel explains:
“For decades, investigators have been putting human or mouse antibodies on viruses, and they haven’t worked – the antibodies would lose their targeting ability.”
He describes the nature of the problem they kept encountering:
“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.”
In their study, Prof. Curiel and colleagues show how – using camelid antibodies – they overcame this problem. They showed that unlike the antibodies of humans, mice and other animals, camelid antibodies can withstand the harsh environment inside cells and retain their ability to find particular cell types.
The team got the idea to use camelid antibodies because they are smaller than those of other animals, and also because studies have shown their “lock” is not the tips of the Y but the stem of the Y – which does not unfold in the harsh environment inside cells.
Prof. Curiel notes:
“We found that when we incorporated the camelid antibodies into the virus, they retained their binding specificity. This opens the door to targeting these antibodies to specific tumor markers.”
There is still a long way to go before the technology is ready for testing in patients. Prof. Curiel says the study demonstrates proof of concept, and that the next step is to develop viruses with camelid antibodies that target a specific tumor and then test them in animals.
Meanwhile, Medical News Today recently reported how researchers are developing soft micro-robots to do biopsies and deliver drugs inside living tissue. Writing in the journal ACS Applied Materials & Interfaces, the developers describe how they made and tested “self-folding microgrippers” that one day could help carry out minimally invasive biopsies or deliver drugs to precise locations inside the body via remote control.