Antibodies Target Cancer's Insides

by Jocelyn Kaiser 

Inside job. When mice with cancer cells that had green fluorescent protein inside them were given antibodies to GFP, they developed fewer lung tumors than control mice did(left).

Credit: Ke Guo et al., Science Translational Medicine, 3 (7 September 2011)

Researchers may have found a way to get inside cancer's head—or at least its body. The cancer cell has been long believed to be impermeable to antibodies that could target it for destruction. But a new study suggests that some antibodies can get through after all, potentially opening up a vast new array of cancer therapies.

When a foreign virus or bacterium enters the body, immune cells start cranking out antibodies, which latch onto the invaders, signaling the immune system to dispatch them. Antibodies can also be used to treat cancer: for example, the breast cancer drug Herceptin is an antibody that targets the HER2 receptor, a protein on the surface of breast tumor cells that spurs cell growth. However, researchers haven't tried to develop drugs against cancer proteins within cells because they thought antibodies were too large to pass through the membrane of most cell types.

The new study defies that conventional wisdom. Cancer biologist Qi Zeng of the Institute of Molecular and Cell Biology in Singapore and collaborators first injected mice with cancer cells so that tumors would begin to form. Two days later, they began injecting the mice twice a week with antibodies to one of two proteins found inside the cancer cells: PRL-3 or mT. Over 17 days, the antibody-treated mice lost weight more slowly and developed fewer metastatic tumors than control mice.

The Singapore team also tried a different strategy: Before giving the mice cancer, they injected either PRL-3 or mT so that their immune system would make its own antibodies against these proteins. That vaccine-style treatment slowed the spread of cancer and, in one experiment, extended the mice's life span by 20%, the team reports today in Science Translational Medicine.

Using antibodies to target intracellular cancer proteins could "expand the scope for tailor-made cancer therapy as well as usher in a new era of tailor-made cancer vaccines," Zeng says. Her team acknowledges, however, that it has not figured out how the treatment works. One possibility is that some of the targeted proteins inside the cancer cells are somehow transported to the surface of the cells, and, as with Herceptin, antibodies latch on and trigger the immune system to kill the cancer cells. Or the antibodies could get into the cancer cells and cause them to self-destruct, as has been observed with some autoimmune diseases.

Immunologist Mark Smyth of the Peter MacCallum Cancer Centre in Melbourne, Australia, is skeptical that the antibodies are really slipping inside cancer cells. The results "are quite heretical in terms of what we know about immunology," he says. Still, cancer researcher Michel Tremblay of McGill University in Montreal, Canada, who studies PRL-3 and related proteins, says the study shows promise. The work is "exciting" because it suggests a more specific way of targeting these internal cellular proteins than so-called small-molecule drugs, he says, which haven't worked well so far.