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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.
AuthorsManabu Kawada, Hiroyuki Inoue, Masunori Kajikawa, Masahito Sugiura, Shuichi Sakamoto, Sakiko Urano, Chigusa Karasawa, Ihomi Usami, Mitsuru Futakuchi, Tohru Masuda
JournalScientific reports (Sci Rep) Vol. 7 Pg. 40400 (01 11 2017) ISSN: 2045-2322 [Electronic] England
PMID28074864 (Publication Type: Journal Article)
Chemical References
  • Antibodies, Monoclonal
  • CLMP protein, human
  • Coxsackie and Adenovirus Receptor-Like Membrane Protein
  • Complement System Proteins
Topics
  • Animals
  • Antibodies, Monoclonal (pharmacology)
  • Antibody-Dependent Cell Cytotoxicity (immunology)
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Clone Cells
  • Complement System Proteins (immunology)
  • Coxsackie and Adenovirus Receptor-Like Membrane Protein (antagonists & inhibitors, metabolism)
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Mice
  • Prostatic Neoplasms (immunology, pathology)
  • Xenograft Model Antitumor Assays

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