CLEC5a-directed bispecific antibody for effective cellular phagocytosis

While antibody-dependent cellular phagocytosis mediated by activating Fc gamma receptor is a key mechanism underlying many antibody drugs, their full therapeutic activities can be restricted by the inhibitory Fc gamma receptor IIB (Fc gamma RIIB). Here, we describe a bispecific antibody approach that harnesses phagocytic receptor CLEC5A (C-type Lectin Domain Containing 5A) to drive Fc gamma receptor-independent phagocytosis, potentially circumventing the negative impact of Fc gamma RIIB. First, we established the effectiveness of such an approach by constructing bispecific antibodies that simultaneously target CLEC5A and live B cells. Furthermore, we demonstrated its in vivo application for regulatory T cell depletion and subsequent tumor regression.

Automated summary

This study describes a bispecific antibody approach that utilizes CLEC5A to drive Fc gamma receptor-independent phagocytosis, potentially overcoming the negative impact of Fc gamma RIIB. The results demonstrate the effectiveness of this approach for tumor treatment.