UW Madison: UW Carbone scientists test novel immunotherapy against melanoma

CONTACT: Lisa Brunette
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Madison, Wis. — A small clinical study in which melanoma tumors were injected with a substance from rabbit blood cells suggests the treatment is safe at low doses and clears the way to test whether it can successfully prompt the immune system to attack the cancer.

The findings of the UW-Madison study were published online in the Journal of Cancer Immunology, Immunotherapy.

Rabbits and other non-primate mammals have a marker (i.e. antigen) in their blood and tissues called α-gal glycolipids. While humans and some monkeys lack this substance, they have plenty of the natural “anti-α-gal” antibodies that can detect it as a foreign substance that should be targeted and rejected. Thus, injecting the tumors with the α-gal glycolipids could allow the immune system’s cancer-fighting cells (i.e. T Cells) to locate and kill the cancer cells. This was the first report of the clinical safety of repeated injections of alpha gal glycolipids within tumors in patients with cancer.

The clinical study was based on earlier laboratory findings and was designed to determine the safety and biological activity of this approach.

Lead author Dr. Mark Albertini, associate professor of medicine (hematology/oncology) and a melanoma specialist at the University of Wisconsin Carbone Cancer, says the two injections, about a month apart, were safe at the doses administered in the study. Detailed blood and tumor studies suggested biological activity of this approach, but the current dose and schedule resulted in only modest effects on the tumors. Additional study of this concept is planned to determine if it can be used to successfully attract T-cells from the immune system to attack the melanoma tumors.

American Cancer Society projects 76,380 new melanoma cases and 10,130 deaths due to melanoma in the United States this year. While new immunotherapy drugs are showing promise against melanoma, not all patients respond to them. Albertini hypothesizes that the injections could work along with the so-called “checkpoint blockade” drugs to recreate a more long-lasting regression of cancer in patients whose disease has spread throughout the body. He hopes to further investigate that concept in a future clinical study.

“This treatment has the theoretical potential to convert treated tumors into “personalized” vaccines, effectively instructing the immune system to recognize tumor cells as cells that ought to be destroyed,” Albertini says.

The small dose-escalation study involved nine patients with advanced melanoma and showed that the treatment was well-tolerated at the doses studied, with minor side effects that included tenderness as well as swelling and redness at the site of the injection. There were no serious whole-body side effects. The monitoring laboratory studies suggested some biological activity of this approach. A biopharmaceutical company called Agalimmune is now developing a synthetic version of the alpha gal technology for subsequent clinical testing.