Breakthrough Strategy for Aggressive Cancer

A laboratory study conducted at Leiden University Medical Center (LUMC) in the Netherlands has found that immunotherapy can be efficiently combined with photodynamic therapy (PDT) to eradicate established tumors. The approach results in strong local tumor destruction and a robust systemic immune response against the disease. The study’s findings are reported online ahead-of-print in the 6 November 2015 issue of the medical journal, Clinical Cancer Research.

“This study is the first step,” states Professor Ferry Ossendorp, the study’s principal investigator. “We are now preparing further preclinical studies with a goal toward achieving clinical acceptance in Western Europe.” Dr. Ossendorp spearheaded the study together with doctoral candidate Jan Willem Kleinovink of LUMC’s Department of Immunohematology and Blood Transfusion, in close collaboration with Dr. Clemens Lowik, now based at Erasmus University Medical Center in Rotterdam.

The researchers focused on a combination of two established therapies, PDT and immunotherapy, in order to eradicate aggressive tumors. PDT entails the use of a special agent, or photosensitizer, along with oxygen and light, to trigger reactions that selectively destroy tumors and render tumors more vulnerable to the immune system. Immunotherapy actually includes a number of strategies aimed at further exploiting various parts and mechanisms of the immune system.

“This combination leads to a broad and effective immune response against established tumors,” says Ossendorp. “We have even observed that distant tumors disappeared in some of the animals.”

The photosensitizing agent used in this study was Bremachlorin, a non-toxic, chlorophyll-derived agent that captures and then transmits light energy for therapeutic purposes. The immunotherapy strategy they chose focused on a peptide-based vaccine that specifically activates the T-cell system against cancer.

The Leiden study used tumor models of two kinds: aggressive lymphoma and aggressive cervical cancer. The study found that Bremachlorin-PDT by itself resulted in a significant slowing of tumor growth in all the test animals. When PDT was combined with a peptide-based vaccine strategy, one third of the mice were completely cured of cancer, meaning that the disease totally disappeared.

Moreover, all of these cured test subjects were fully protected against the subsequent development of the same type of cancer. And finally, the combination treatment of primary tumors led to the eradication of distant secondary tumors, or metastases. This exceptional finding will require further study, Ossendorp notes. Metastatic disease is the number one cause of cancer-related death.

The researchers concluded that Bremachlorin-PDT, together with the long peptide vaccine strategy, produced a potent whole-body immune response against the aggressive malignancies. In their report for Clinical Cancer Research, they note that the photoimmune strategy of blending immunotherapy with Bremachlorin-PDT offers “a feasible novel treatment strategy for advanced cancer.”

Since 2006, Bremachlorin® has been approved for clinical use in Russia (under the name Radachlorin®) and has conditional approval in South Korea. Preclinical studies are under way in the Netherlands with a goal toward achieving clinical acceptance in Europe. “After completion of our preclinical studies, we hope to coordinate clinical studies of cancer patients in the EU and hopefully get approval for using this combined treatment strategy here in the EU,” Ossendorp states.