Okayama University successfully eliminates tumors solely through light irradiation: Intracellular alkalization offers hope for new treatment with fewer side effects

A joint research group consisting of Professor Yuki Sudo and Lecturer Keiichi Kojima from the Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Doctoral Student Shin Nakao, a fourth-year doctoral student at the Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Professor Yosuke Togashi, Professor Hideyo Ohuchi and Assistant Professor Keita Sato from the Faculty of Medicine, Dentistry and Pharmaceutical Sciences at Okayama University and Medical Staff Naoya Kemmotsu from Okayama University Hospital (Department of Neurological Surgery) has successfully used light to selectively eliminate cancer tumors in mice by utilizing a protein that alkalizes cells in response to light. In the future, this achievement is expected to lead to a new phototherapy for cancer with fewer side effects, capable of selectively removing only human cancer cells. Their research was published in the electronic edition of JACS and selected for the journal cover.

The research group has previously developed technology to selectively eliminate specific cells using light as a foundation for cancer therapy with fewer side effects. Specifically, they revealed that by using animal cells to synthesize the light-sensitive protein Archaerhodopsin-3 (abbreviated as AR3), which has the function of alkalizing cells, and irradiating light, spontaneous cell death could be induced only in targeted cells.

This time, they further developed this technology and verified "whether it is possible to selectively eliminate" cancer cells existing in mouse bodies using light.

After introducing genes into cancer cells derived from colon cancer and malignant melanoma to synthesize AR3, they transplanted them into mice to form tumors. When the tumors were irradiated with green light for one hour, cancer cell death began. Meanwhile, they found that immune cells that suppress cancer growth showed almost no phototoxicity and maintained normal function. Furthermore, when measuring tumor size after light irradiation, it was ascertained that tumor volume gradually decreased and had almost disappeared by the seventh day after light irradiation.

These results demonstrated that irradiating cancer tumors with light induces individual cell death, leading to efficient elimination of the entire tumor. In other words, they succeeded in selectively eliminating cancer tumors existing in living mouse bodies using light.

Technology to eliminate cancer cells is essential for cancer treatment, but existing methods alone have limits in the scope of treatment. In recent years, advances in optical technologies such as LEDs and lasers have made it possible to irradiate light to only specific sites in the body, and phototherapy methods used clinically, such as photoimmunotherapy, have been developed. The application to humans of the method demonstrated in mice, that is to selectively eliminate cancer cells with light and inducing tumor remission, is attracting attention as it could lead to a new type of cancer therapy that minimizes impact on surrounding normal cells.

Nakao commented: "We succeeded in eliminating cancer cells in mouse bodies using light. This is a cancer therapy with fewer side effects, so I hope this technology will contribute to future cancer medicine."

Journal Information
Publication: JACS
Title: Optogenetic Cancer Therapy Using the Light-Driven Outward Proton Pump Rhodopsin Archaerhodopsin-3 (AR3)
DOI: 10.1021/jacs.5c13053