Researchers at UT Southwestern Medical Center have developed a method to screen thousands of peptoids for specific characteristics, potentially providing a cheaper alternative to therapeutic antibodies.
The researchers screened about 300,000 peptoids to see which ones would interact with VEGFR2, a type of molecule on the surface of human cells. VEGFR2 is essential in creating new blood vessels through interaction with the hormone VEGF, which is normally a helpful process but is harmful to the body when the new blood vessels are nourishing a growing tumor.
A commercially produced antibody is used to treat some cancers by blocking the VEGF-VEGFR2 interaction and thus starving the tumor, but it costs a patient about $20,000 a year, Dr. Kodadek [Dr. Thomas Kodadek, chief of translational research at UT Southwestern, and a senior author of the study] said.
The new screening technology involves hundreds of thousands of peptoids, bound to tiny plastic beads. In the study, the cells with VEGFR2 were labeled to fluoresce red and those lacking VEGFR2 were labeled to fluoresce green. After exposing the beads to the mixture of cells, the beads were examined under a fluorescent microscope. Those bound to red cells — the ones with VEGFR2 — were collected.
This screen, which took a couple of days, isolated five peptoids out of approximately 300,000 screened, showing that the process was an effective way to quickly narrow down a search, Dr. Kodadek said.
The researchers further tested one of the five peptoids that bound most tightly to VEGFR2 and found that it blocked VEGFR2’s action in cultured cells. When they gave it in low doses to mice with implanted human bone- and soft-tissue cancer, the peptoid slowed the growth of the tumors and reduced the density of blood vessels leading to them.