Much as a hybrid bicycle is a cross between two bikes--a road bike frame with mountain bike handlebars, for instance--this hybrid compound is a cross between two molecules. One is a traditional anticancer drug, a small molecule that targets cancer tumors. The other is a type of antibody, which is a protein produced in great abundance by the bodys immune system and found naturally in the bloodstream.
The hybrid of the two, described in an upcoming issue of the journal Proceedings of the National Academy of Sciences, was found to have a profound effect on the size of tumors in mouse models--shrinking tumors of both Kaposi's sarcoma and colon cancers in these preclinical studies. Moreover, this approach is general enough that it could be used to design hybrids against any number of cancers.
"A single antibody can become a whole multiplicity of therapeutics simply by mixing it with the desired small molecule," says TSRI Professor Carlos F. Barbas III, Ph.D., who is Janet and W. Keith Kellogg II Chair in Molecular Biology. Barbas conducted the research with TSRI President Richard A. Lerner, M.D., and several colleagues at TSRI's Skaggs Institute for Chemical Biology.
Steering and Support, Joined at the Hip
The TSRI team built the hybrid molecule with a "catalytic" antibody, a small drug molecule, and a linker molecule that joins the two. The hybrid thus formed borrows the wheels and the frame of the antibody for supports and the handlebars of the small drug molecule for steering ability.
Also called immunoglobulins, antibodies are proteins produced by immune cells that are designed to recognize a wide range of foreign pathogens. After a bacterium, virus, or other pathogen enters the bloodstream,
Contact: Jason Bardi
Scripps Research Institute