November 2004

Modular Drugs

By Karen Epper Hoffman

Over the past decade, biotech companies have introduced a string of protein-based antibody drugs, which mimic the action of the body's own immune system to combat conditions like cancer and arthritis. Antibody drugs can zero in precisely on misbehaving cells and often enlist the aid of our own antibodies to force a disease into retreat. But there's a price for their effectiveness. Antibody drugs are based on large molecules, so they have a hard time getting into the bloodstream and into cells.

Over the past year, however, researchers have begun to test a new class of genetically engineered protein drugs that act like antibody drugs but are more easily absorbed into the body. They're called small modular immunopharmaceuticals, or SMIPs, and their main proponent is Seattle-based Trubion Pharmaceuticals. "The basic idea was, 'How do we make these molecules smaller'" without diminishing their effects? says Daniel Burge, Trubion's senior vice president of clinical development.

The drugs Trubion's researchers eventually devised are one-third to two-thirds the size of conventional antibody drugs. They can also be adapted to the needs of specific patients: sections of the molecules can be added or removed to hit offending cells with larger or smaller payloads, depending on the treatment required.

Trubion's most advanced drug, which will enter safety trials in humans early in 2005, attacks white blood cells called B cells, which can cause diseases like lymphoma and leukemia when they become malignant. One end of the drug molecule binds specifically to B cells, while the other end carries a module that invites other immune cells to attack the B cells. Nancy Haigwood, viral-vaccines program director at the Seattle Biomedical Research Institute, says that based on the data she has seen on Trubion's drugs, "It's possible that for particular applications they might even replace [current antibody drugs] because they are smaller, nimbler, and better at getting to the cells. It looks like it has terrific potential."