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Fc-Binding Antibody-Recruiting Molecules for Cancer Therapy: Exploiting Endogenous IgG Without antigen–Fab Interactions

submitted on 08.10.2019, 05:39 and posted on 11.10.2019, 21:09 by Koichi Sasaki, Minori Harada, Yoshiki Miyashita, Hiroshi Tagawa, Akihiro Kishimura, Takeshi Mori, Yoshiki Katayama

Small molecules emulating the effector functions of antibodies have potential clinical benefits because of their low immunogenicity. Antibody-recruiting molecules (ARMs) are bispecific molecules designed to redirect endogenous antibodies to targets. However, endogenous antibodies show intra/inter-patient differences regarding their concentrations and affinities, limiting the potential of ARMs. We sought to address this issue using a Fc-binding peptide instead of an antigen for antibody redirection. Fc-binding ARM (Fc-ARM) targeting folate receptor-α (FR-α) expressed on cancer cells, formed a ternary complex of Fc-ARM, FR-α, and antibody on cancer cells. The ability of this ternary complex to activate natural killer cells was positively correlated with its Fc affinity, and did not require the Fab region. Fc-ARM hitchhiked on pooled human IgG to enhance its blood retention, and suppressed tumor growth in a mouse xenograft model of human cancer. Thus, Fc-ARM has the potential to be employed as a less immunogenic alternative to therapeutic antibodies.


Research Fellowship for Young Scientists (JSPS, 17J05032)


Email Address of Submitting Author


Kyushu University



ORCID For Submitting Author


Declaration of Conflict of Interest

Authors declare no competing financial interests.

Version Notes

v1 (original)