| Literature DB >> 33357423 |
Futa Mimoto1, Kanako Tatsumi2, Shun Shimizu3, Shojiro Kadono4, Kenta Haraya3, Miho Nagayasu3, Yuki Suzuki3, Etsuko Fujii3, Masaki Kamimura5, Akira Hayasaka3, Hiroki Kawauchi4, Kazuhiro Ohara4, Masayuki Matsushita6, Takeshi Baba4, Hiroaki Susumu3, Takuya Sakashita3, Terushige Muraoka4, Kosuke Aso3, Hitoshi Katada3, Eriko Tanaka4, Kenji Nakagawa3, Masami Hasegawa4, Miho Ayabe4, Tessai Yamamoto3, Shigero Tanba4, Takahiro Ishiguro7, Takayuki Kamikawa4, Takeru Nambu8, Tatsuya Kibayashi4, Yumiko Azuma4, Yasushi Tomii3, Atsuhiko Kato3, Kazuhisa Ozeki3, Naoaki Murao3, Mika Endo4, Junichi Kikuta9, Mika Kamata-Sakurai7, Masaru Ishii9, Kunihiro Hattori4, Tomoyuki Igawa10.
Abstract
The extracellular adenosine triphosphate (ATP) concentration is highly elevated in the tumor microenvironment (TME) and remains tightly regulated in normal tissues. Using phage display technology, we establish a method to identify an antibody that can bind to an antigen only in the presence of ATP. Crystallography analysis reveals that ATP bound in between the antibody-antigen interface serves as a switch for antigen binding. In a transgenic mouse model overexpressing the antigen systemically, the ATP switch antibody binds to the antigen in tumors with minimal binding in normal tissues and plasma and inhibits tumor growth. Thus, we demonstrate that elevated extracellular ATP concentration can be exploited to specifically target the TME, giving therapeutic antibodies the ability to overcome on-target off-tumor toxicity.Entities:
Keywords: extracellular ATP; oncometabolite; purinergic signaling; therapeutic antibody; tumor microenvironment; tumor targeting
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Year: 2020 PMID： 33357423 DOI： 10.1016/j.celrep.2020.108542
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423