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May 22, 2018 - MCI Research Shorts: Cutting-edge research stands to double immunotherapy response rate

Dr. Art FrankelMOBILE, Alabama -- Cutting-edge research at USA Mitchell Cancer Institute stands to double the response rate to immunotherapy without increasing side effects, but the effort’s lead investigator needs the immediate help of Gulf Coast cancer patients to determine if customized gut bacteria and nutrition regimens provide the immunotherapy boost he suspects.

“Right now, a little more than 30 percent of patients can be put into long-term remission with this immunotherapy. We believe with the right probiotics and nutrition, we can more than double that to about 75 percent,” said Dr. Arthur E. “Art” Frankel, MCI chief of medical oncology and inaugural holder of the Arlene and Mayer Mitchell Chair in Medical Oncology.

Frankel, an Austin, Texas native, who earned his medical degree from Harvard University, completed a research postdoctoral fellowship at the National Institutes of Health and a residency and medical oncology fellowship at Stanford University. Nationally renowned for his melanoma research, he is co-inventor on 12 issued patents and has authored or co-authored more than 200 publications in peer-reviewed journals.

“The more information you have, the more accurate your selection of the right probiotics and nutrition can be, but I need to get this information from patients, and that requires collecting stool samples, so we can know all of the DNA present and help design a better path forward – and ultimately better responses – for these patients,” he said.

Specifically, Frankel works with antibodies that unlock T cells, a subtype of white blood cells critical to cell-instigated immunity. About 15 years ago, he explained, researchers determined normal T cells are reined in by immune checkpoints that prevent all people from suffering from autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and lupus. The downside is that the checkpoints make it more difficult for T cells to fight cancer leading to tumor growth.

Antibodies have been developed, however, that remove the immune checkpoints, unlock T cells and allow them to attack tumors with high mutation burdens. At the moment, somewhere between 30 percent and 50 percent of cancer patients respond to this approach, but certain types of cancers are resistant, and a percentage of patients still don’t respond when immune checkpoint blockades, or antibodies, are administered, Frankel said.

The epidermis, or top layer of the skin, is comprised primarily of three types of cells: squamous cells, basal cells and melanocytes. As the name implies, melanocytes produce a brown pigment called melanin, the concentration of which determines the darkness of a person’s skin. Melanoma is a type of cancer that begins specifically in the melanocytes, and although far less common than basal cell and squamous cell skin cancers, melanoma is more dangerous because of its likelihood to spread to other parts of the body if not detected early.  According to the American Cancer Society, cancer of the skin is the most common of all cancers, and May is recognized as Melanoma and Skin Cancer Awareness Month.

While melanoma accounts for only about 1 percent of all skin cancers, the ACS attributes the large majority of skin cancer deaths to melanoma and notes the overall melanoma diagnosis rate has increased steadily over the past 30 years. Of the estimated 91,270 new melanoma cases expected to be diagnosed in the U.S. in 2018, roughly 60 percent will be in men and slightly less than 40 percent will be in women. Meanwhile, men are expected to account for roughly 64 percent of the estimated 9,320 melanoma-related deaths projected in the United States in 2018.

At present, Frankel said there are two primary approaches for treating patients whose cancer does not respond automatically to autoimmune therapy. The first involves administering drugs alongside the antibodies to alter resistance pathways, but certain types of drugs affect pathways that are vital to other bodily functions, and the complementary drug regimen tends to compound side effects. In addition, those treatments can be expensive creating an added barrier to treatment.

“It’s hard to stay ahead of something that is living and growing and mutating, but there is a gentler approach. It turns out we have the ability to modulate our own immune system. It turns out (that) diet and the bacteria in your gut can allow your body to activate your immune system to fight melanoma better,” he said, noting the affordability and simplicity make the approach more appealing to a broader patient base.

Frankel has led cancer research and clinical programs for three decades across the South, most recently overseeing Phase I clinical trials at the University of Texas Southwestern Medical Center in Dallas. He is also former executive director of the Cancer Research Institute at Scott & White Hospital / Texas A&M School of Medicine and served at Wake Forest University, the Medical University of South Carolina, the Florida Hospital Cancer and Leukemia Research Center, and Duke University.

For more information on how to participate in Frankel’s research, call him directly at (254) 718-0781 or contact Sarah Fillingam at (251) 689-2010.


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