title: A novel monoclonal antibody targeting coxsackie virus and adenovirus receptor inhibits tumor growth in vivo.
abstract: To create a new anti-tumor antibody, we conducted signal sequence trap by retrovirus-meditated expression method and identified coxsackie virus and adenovirus receptor (CXADR) as an appropriate target. We developed monoclonal antibodies against human CXADR and found that one antibody (6G10A) significantly inhibited the growth of subcutaneous as well as orthotopic xenografts of human prostate cancer cells in vivo. Furthermore, 6G10A also inhibited other cancer xenografts expressing CXADR, such as pancreatic and colorectal cancer cells. Knockdown and overexpression of CXADR confirmed the dependence of its anti-tumor activity on CXADR expression. Our studies of its action demonstrated that 6G10A exerted its anti-tumor activity primarily through both antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Moreover, 6G10A reacted with human tumor tissues, such as prostate, lung, and brain, each of which express CXADR. Although we need further evaluation of its reactivity and safety in human tissues, our results show that a novel anti-CXADR antibody may be a feasible candidate for cancer immunotherapy.
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Numazu, Microbial Chemistry Research Foundation, 18-24 Miyamoto, Numazu-shi, Shizuoka 410-0301, Japan.|Institute of Microbial Chemistry (BIKAKEN), Laboratory of Oncology, Microbial Chemistry Research Foundation, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Kawada
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Numazu, Microbial Chemistry Research Foundation, 18-24 Miyamoto, Numazu-shi, Shizuoka 410-0301, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Inoue
authors.affiliation: Medical &Biological Laboratories Co., Ltd., 4-5-3 Sakae, Naka-ku, Nagoya, Aichi 460-0008, Japan.
authors.forename: Masunori
authors.initials: M
authors.lastname: Kajikawa
authors.affiliation: Medical &Biological Laboratories Co., Ltd., 4-5-3 Sakae, Naka-ku, Nagoya, Aichi 460-0008, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Sugiura
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Numazu, Microbial Chemistry Research Foundation, 18-24 Miyamoto, Numazu-shi, Shizuoka 410-0301, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Sakamoto
authors.affiliation: Medical &Biological Laboratories Co., Ltd., 4-5-3 Sakae, Naka-ku, Nagoya, Aichi 460-0008, Japan.
authors.forename: Sakiko
authors.initials: S
authors.lastname: Urano
authors.affiliation: Medical &Biological Laboratories Co., Ltd., 4-5-3 Sakae, Naka-ku, Nagoya, Aichi 460-0008, Japan.
authors.forename: Chigusa
authors.initials: C
authors.lastname: Karasawa
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Numazu, Microbial Chemistry Research Foundation, 18-24 Miyamoto, Numazu-shi, Shizuoka 410-0301, Japan.
authors.forename: Ihomi
authors.initials: I
authors.lastname: Usami
authors.affiliation: Department of Molecular Toxicology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Futakuchi
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Numazu, Microbial Chemistry Research Foundation, 18-24 Miyamoto, Numazu-shi, Shizuoka 410-0301, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Masuda
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002999:Clone Cells; D003165:Complement System Proteins / Q000276:immunology; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000276:immunology / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; C568771:CLMP protein, human; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D003165:Complement System Proteins