Exploitation of Elevated Extracellular ATP to Specifically Direct Antibody to Tumor Microenvironment

• DOI: 10.1016/j.celrep.2020.108542
• Publication Date: 2020-12-22T16:51:46Z
• Authors: Futa Mimoto; Kanako Tatsumi; Shun Shimizu; Shojiro Kadono; Kenta Haraya; Miho Nagayasu; Yuki Suzuki; Etsuko Fujii; Masaki Kamimura; Akira Hayasaka; Hiroki Kawauchi; Kazuhiro Ohara; Masayuki Matsushita; Takeshi Baba; Hiroaki Susumu; Takuya Sakashita; Terushige Muraoka; Kosuke Aso; Hitoshi Katada; Eriko Tanaka; Kenji Nakagawa; Masami Hasegawa; Miho Ayabe; Tessai Yamamoto; Shigero Tanba; Takahiro Ishiguro; Takayuki Kamikawa; Takeru Nambu; Tatsuya Kibayashi; Yumiko Azuma; Yasushi Tomii; Atsuhiko Kato; Kazuhisa Ozeki; Naoaki Murao; Mika Endo; Junichi Kikuta; Mika Kamata-Sakurai; Masaru Ishii; Kunihiro Hattori; Tomoyuki Igawa
• Keywords: Adenosine triphosphate

The extracellular adenosine triphosphate (ATP) concentration is highly elevated in the tumor microenvironment (TME) and remains tightly regulated normal tissues. Using phage display technology, we establish a method to identify an antibody that can bind antigen only presence of ATP. Crystallography analysis reveals ATP bound between antibody-antigen interface serves as switch for binding. In transgenic mouse model overexpressing systemically, binds tumors with minimal binding tissues plasma inhibits growth. Thus, demonstrate be exploited specifically target TME, giving therapeutic antibodies ability overcome on-target off-tumor toxicity.