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Fc-Binding Antibody-Recruiting Molecules Targeting Prostate-Specific Membrane Antigen: Defucosylation of Antibody for Efficacy Improvement

submitted on 15.07.2020, 01:49 and posted on 15.07.2020, 11:52 by Koichi Sasaki, Minori Harada, Takuma Yoshikawa, Hiroshi Tagawa, Yui Harada, Yoshikazu Yonemitsu, Taka-aki Ryujin, Akihiro Kishimura, Takeshi Mori, Yoshiki Katayama

Synthetic small molecules that redirect endogenous antibodies to target cells are promising drug candidates because they overcome the potential shortcomings of therapeutic antibodies, such as immunogenicity. Previously, we reported a novel class of bispecific molecules targeting the antibody Fc region and folate receptor, named Fc-binding antibody-recruiting molecules (Fc-ARMs). Fc-ARMs can theoretically recruit most endogenous antibodies, inducing cancer cell elimination via antibody-dependent cell-mediated cytotoxicity (ADCC). Here, we describe new Fc-ARMs that target prostate cancer (Fc-ARM-Ps). Fc-ARM-Ps recruited antibodies to cancer cells expressing prostate membrane-specific antigen but did so with lower efficiency compared with Fc-ARMs targeting folate receptor. Upon recruitment by Fc-ARM-P, defucosylated antibodies efficiently activated natural killer cells and induced ADCC, whereas antibodies with intact N-glycans did not. The results suggest that the affinity between recruited antibodies and CD16a, a type of Fc receptor expressed on immune cells, could be a key factor controlling immune activation in the Fc-ARM strategy.


Challenging Research (Exploratory) of MEXT, Japan (18K19148)

Research Fellowship for Young Scientists, Japan Society for the Promotion of Science (17J05032, 17J04646)


Email Address of Submitting Author


Kyushu University



ORCID For Submitting Author


Declaration of Conflict of Interest

The authors declare no competing financial interests.