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Sabotage as therapy: Aiming lupus antibodies at vulnerable cancer cells

Date:
September 2, 2014
Source:
Yale University
Summary:
Researchers may have discovered a new way of harnessing lupus antibodies to sabotage cancer cells made vulnerable by deficient DNA repair. The study 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.

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. 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," Hansen said.

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. 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," said 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," Hansen said.


Story Source:

The above story is based on materials provided by Yale University. The original article was written by Vicky Agnew. Note: Materials may be edited for content and length.


Journal Reference:

  1. Philip W. Noble, Melissa R. Young, Sasha Bernatsky, Richard H. Weisbart, James E. Hansen. A nucleolytic lupus autoantibody is toxic to BRCA2-deficient cancer cells. Scientific Reports, 2014; 4 DOI: 10.1038/srep05958

Cite This Page:

Yale University. "Sabotage as therapy: Aiming lupus antibodies at vulnerable cancer cells." ScienceDaily. ScienceDaily, 2 September 2014. <www.sciencedaily.com/releases/2014/09/140902151302.htm>.
Yale University. (2014, September 2). Sabotage as therapy: Aiming lupus antibodies at vulnerable cancer cells. ScienceDaily. Retrieved September 16, 2014 from www.sciencedaily.com/releases/2014/09/140902151302.htm
Yale University. "Sabotage as therapy: Aiming lupus antibodies at vulnerable cancer cells." ScienceDaily. www.sciencedaily.com/releases/2014/09/140902151302.htm (accessed September 16, 2014).

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