Two postdocs, Davoud Ahmadvand and Ladan Parhamifar, from the Faculty of Pharmaceutical Sciences, University of Copenhagen, were also involved in the lab work.
Size and properties matter
Compared to other protein-based drugs, nanobodies are very small. They are ten times smaller than intact antibodies. They are also less sensitive to temperature and pH changes and can be easily linked to nanoparticles and other proteins. These properties make nanobodies very interesting for targeting of cancer cells.
The recently published article in Journal of Controlled Relase describes how a Mucin-1 nanobody was linked to specialised nanoparticles made from polymers carrying a killer gene known at truncated-Bid. When expressed, the gene product triggers cells to commit suicide.
However, the expression of the killer gene was under the control of the cancer-specific Mucin-1 promoter as to avoid non-specific cell killing. These procedures are also referred to as "transcriptional targeting", which can prevent normal tissue toxicities associated with other cancer treatments. Indeed, the formulation proved to be highly effective in killing cancer cells expressing the Mucin-1 marker, while no harm was done to the normal cells or cancer cells that did not express the Mucin-1 marker.
The efficacy of these nanoparticles is now being tested in animal models.
Another exciting development is that the team has now purified a second and a highly effective nanobody against another cancer marker (Her-2) expressed by certain breast tumors.
|Contact: Moein Moghimi|
University of Copenhagen