title: Establishment of monoclonal antibodies against cell surface domains of ASCT2/SLC1A5 and their inhibition of glutamine-dependent tumor cell growth.
abstract: Human alanine-serine-cysteine transporter 2 (ASCT2; SLC1A5) is a major transporter of the amino acid glutamine that is known to be overexpressed in certain malignant tumors. In this study, we generated specific monoclonal antibodies (MAbs) against ASCT2 by establishing an ASCT2-expressing Chinese hamster ovary cell line that was used to immunize mice and rats. The MAbs KM4008, KM4012, and KM4018 against ASCT2 were isolated through a cell-based screen; these specifically bound to ASCT2-positive cells, as determined by flow cytometry and immunoprecipitation. In addition, the antibodies suppressed glutamine-dependent growth of WiDr colorectal cancer cells. These results provide evidence supporting the use of MAbs against ASCT2 as an effective therapeutic strategy for cancer treatment.
authors.affiliation: R&D Division, Tokyo Research Park, Kyowa Hakko Kirin Co., Ltd, Machida-shi, Tokyo, Japan.
authors.forename: Masayo
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: R&D Division, Tokyo Research Park, Kyowa Hakko Kirin Co., Ltd, Machida-shi, Tokyo, Japan.
authors.forename: Hiroe
authors.initials: H
authors.lastname: Toki
authors.affiliation: R&D Division, Tokyo Research Park, Kyowa Hakko Kirin Co., Ltd, Machida-shi, Tokyo, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Furuya
authors.affiliation: R&D Division, Tokyo Research Park, Kyowa Hakko Kirin Co., Ltd, Machida-shi, Tokyo, Japan. Electronic address: hiroshi.ando@kyowa-kirin.co.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ando
mesh_terms: D026962:Amino Acid Transport System ASC / Q000737:chemistry*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry*; D016466:CHO Cells; D049109:Cell Proliferation; D006224:Cricetinae; D003412:Cricetulus; D000939:Epitopes / Q000737:chemistry; D006801:Humans; D051379:Mice; D015778:Minor Histocompatibility Antigens / Q000737:chemistry*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D000072417:Protein Domains; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D026962:Amino Acid Transport System ASC; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000939:Epitopes; D015778:Minor Histocompatibility Antigens; C420506:SLC1A5 protein, human
keywords: ASCT2; Glutaminolysis; Monoclonal antibody; SLC1A5