Preserving healthy cells while human-derived antibodies fight cancer cells is now possible, a new research has revealed.
Duke Health researchers were able to develop from the immune system of humans an antibody that targets natural defense mechanisms, which cancer cells use as protection. Cancer cells are often hard to eliminate because they exploit the body's proteins which prevent immune response activation.
Senior author and Duke University Department of Pharmacology and Cancer Biology professor Edward F. Patz, Jr., said their technique differs from other immunotherapeutic approaches because the antibody is derived from the human body. The antibody weakens the cancer cells' defense system before attacking it.
A past study showed that cancer cells force healthy cells to release growth signals that hasten the spread of the disease.
The present study stemmed from the fact that a number of patients with lung cancer have tumors that do not become advanced diseases. These lung cancer patients were noted to have antibodies for complement factor H (CFH), which inhibits the complement C3b to deposit on the surface of the cell. Complement C3b causes cell membrane degradation.
Patz and his team set out to identify the CFH antibody and explored how the elicited immune response might be adapted for cancer therapeutics. One of the challenges the team had to face was the production of mature antibodies that would identify the precise CFH produced by autoantibodies during early stages of cancer.
To address this challenge, the team collected and isolated CFH antibody-producing white blood cells of cancer patients. They proceeded to clone the antibody genes coming from one immune cell such that the patient's immune system preferentially attacked cancer cells. The healthy cells remained unaffected.
The antibodies were tested on lung, breast, and gastric cancer cell lines in laboratory cultures and in live mice tumors. The results showed that the generated antibodies were able to kill only tumor cells without any adverse effects. An additional adaptive immune response was likewise generated when the disrupted cells activated a group of lymphocytes, which produced a more serious systemic attack.
Patz said the adaptive cellular response should be further examined because he believes it would have a tremendous impact on long-term cancer outcomes.
"This could represent a whole new approach to treating cancer, and it's exciting because the antibody selectively kills tumor cells, so we don't have significant side effects to achieve tumor control," said Patz. "We believe we can modulate the immune response and let the body's own immune system take over to either kill the tumor or keep it from growing."
The study was published in Cell Reports on May 5.
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