Establishment of a Monoclonal Antibody against Human NTCP That Blocks Hepatitis B Virus Infection
Toshitada Takemori, Akiko Sugimoto-Ishige, Hironori Nishitsuji, Yushi Futamura, Michishige Harada, Tomomi Kimura‐Someya, Takehisa Matsumoto, Teruki Honma, Miho Tanaka, Masami Yaguchi, Kyoichi Isono, Haruhiko Koseki, Hiroyuki Osada, Daiki Miki, Takashi Saito, Takashi Tanaka, Takehiro Fukami, Toshio Goto, Mikako Shirouzu, Kunitada Shimotohno, Kazuaki Chayama
Abstract
A number of entry inhibitors are being developed to enhance the treatment of HBV patients with oral nucleoside/nucleotide analogues (NA). To amplify the effectiveness of NA therapy, several efforts have been made to develop therapeutic MAbs with neutralizing activity against HBs antigens. However, the neutralizing effect of these MAbs may be muted by a large excess of HBsAg-positive noninfectious particles in the blood of infected patients. The advantage of NTCP-targeted HBV entry inhibitors is that they remain effective regardless of viral genotype, viral mutations, and the presence of subviral particles. Although N6HB426-20 requires a higher dose than myrcludex to obtain equivalent suppression of HBV in a model mouse system, it maintained the inhibitory effect for a long time postadministration in proportion to the half-life of an IgG MAb. We believe that further improvements will make this antibody a promising treatment option for patients with chronic hepatitis B.