Yale Cancer Center researchers may have discovered a new way of harnessing lupus antibodies to sabotage cancer cells made vulnerable by deficient DNA repair. The findings were published recently in Nature‘s journal Scientific Reports.
The study, led by James E. Hansen, M.D., assistant professor of therapeutic radiology at Yale School of Medicine, found that cancer cells with deficient DNA repair mechanisms (or the inability to repair their own genetic damage) were significantly more vulnerable to attack by lupus antibodies.
“Patients with lupus make a wide range of autoantibodies that attack their own cells and contribute to the signs and symptoms associated with lupus,” Dr. Hansen explains. “Some of these antibodies actually penetrate into cell nuclei and damage DNA, and we suspected that we may be able to harness the power of these antibodies for use in targeted cancer therapy.”
The genetic code that determines how a cell develops is written in DNA. Damage to this code can cause a cell to malfunction, die, or transform into a cancer cell. Normal cells are equipped to repair damaged DNA and preserve the genetic code, but many cancer cells have defective DNA repair machinery and accumulate genetic mutations.
This difference between normal cells and certain cancer cells creates an opportunity to develop therapies that damage DNA and only kill cancer cells that cannot repair the damage. However, DNA is sequestered inside cell nuclei, where delivery of therapies can be challenging. Now, Yale Cancer Center researchers are finding that naturally occurring lupus antibodies just may be a solution to this problem.
“Lupus antibody-based cancer therapy is an emerging new concept, and I believe we are just seeing the tip of the iceberg in terms of the potential of this approach,” says Dr. Hansen.
The researchers previously found that a lupus antibody called 3E10 inhibits DNA repair and sensitizes cancer cells to DNA damage, and they have now found that the DNA-damaging lupus antibody 5C6 is toxic to DNA repair-deficient cancer cells.
“Now that we know that more than one lupus antibody has a selective effect on cancer cells, I am confident that additional lupus autoantibodies with even greater therapeutic potential await discovery,” says Dr. Hansen.
The team also notes that their findings raise the possibility that lupus autoantibodies may be partly responsible for the unexpectedly low rates of breast, ovarian, and prostate cancers observed in lupus patients.
“This study provides the basis for the potential use of a lupus anti-DNA antibody in cancer therapy and identifies lupus autoantibodies as a potentially rich source of therapeutic agents,” they conclude.
In a related study published in June, scientists discovered that certain autoimmune diseases may share a pathogenic link with cancer. The findings have opened up a new line of research exploring novel treatment options for the rare condition myasthenia gravis.