Nature Medicine | Spoonful of Medicine

Lupus antibodies may provide new option for cancer therapies

Radiation and chemotherapy are sometimes not strong enough to conquer aggressive tumors, but a new method promises to help cancer treatment become more effective. The approach uses antibodies produced by the body when a person has lupus, an autoimmune disorder that can affect the skin, joints, and other organs. These lupus antibodies can weaken cancerous cells by penetrating the cells’ nuclei and disrupting their DNA, priming the cells for destruction by radiation or chemotherapy, according to a preliminary study published in Science Translational Medicine on 24 October.

“It’s remarkable that an antibody could have this ability to penetrate a living cell,” says Jim Ford, an oncologist at the Stanford University School of Medicine in California, who authored a commentary piece on the paper. “It’s a totally new therapeutic approach.”

In the study, researchers implanted mice with breast cancer and brain cancer, and then gave the animals a one-time dose of lupus antibody. The scientists had isolated the antibody from cells from another group of mice that had been manipulated to have a rodent version of lupus. They followed the antibody injection with radiation in one experiment, and with chemotherapy in another test. In both experiments, the mice treated with the antibody showed significantly stronger response to the secondary treatment compared to the group receiving only radiation or chemotherapy.

For example, in the radiation experiment, the scientists considered the rate at which the tumors tripled in size. They found tumors treated with the antibody grew more slowly, taking 5.7 days longer (13.7 days total) to triple than tumors not treated with the antibody, which tripled after just 8 days. The treatment was also successful in human cells in a dish, according to study author Peter Glazer, a radiologist at the Yale University School of Medicine in New Haven, Connecticut .

The breast cancer drug avastin (bevacizumab) is another monoclonal antibody that weakens tumors prior to treatment with radiation or chemotherapy. Avastin works by cutting off cancer cells’ supply of nutrients or oxygen.

Lupus antibodies are unique in their ability to enter cells to attack DNA, says Glazer. Antibodies are typically large, so “99.99 percent of all antibodies just can’t get into cells,” he explains. But lupus antibodies attach themselves to nucleotide precursors floating outside the cell, ultimately “riding in on the shoulders of the nucleotide precursors,” he says.

His team also showed that the lupus antibody can work on its own to kill certain cancers resulting from BRCA-gene mutations, such as breast, ovarian or prostate cancer. People with lupus have around a 30% reduced rate of BRCA-related cancers, evidence suggests

Glazer is confident the antibody will be safe in humans because another group of researchers had tested these antibodies as a therapeutic vaccine against lupus itself. Although the clinical trial ultimately failed to treat the autoimmune disease, it did not yield side effects.

Ford agrees that knowing the safety profile is helpful. “Unlike most new drugs, this actually has been [tested] in humans,” he says.

Notably, however, the cancer therapy differs from the experimental lupus vaccine because the cancer therapy will use higher doses over a longer period of time. Humans can only tolerate a small amount of an antibody that is derived from a mouse, so the drug must be “humanized” for long-term use, says Glazer. Researchers will modify the DNA of the engineered antibody so it resembles that of a human more than a mouse, a common practice, according to Glazer.

If all goes smoothly in terms of receiving funding and industry support, Glazer says he expects clinical trials of the lupus antibody as a supplemental cancer treatment in three years.


There are currently no comments.