ChemRxiv
These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
1/1
2 files

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

preprint
submitted on 15.07.2020 and posted on 15.07.2020 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.

Funding

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

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

History

Email Address of Submitting Author

edrcsk201@gmail.com

Institution

Kyushu University

Country

Japan

ORCID For Submitting Author

0000-0001-9966-957X

Declaration of Conflict of Interest

The authors declare no competing financial interests.

Exports