Mechanistically, the anti-tumor activity of anti-RANKL/PD-1 BsAb required CD8 + T cells, host PD-1 and IFNγ. Targeting RANKL and PD-1 simultaneously within the tumor microenvironment (TME) improved anti-tumor efficacy compared with combination of two separate mAbs.How is anti-RANKL/PD-1 BSAB made?
A anti-RANKL/PD-1 BsAb was generated which binds to both muRANKL and muPD-1 by fusing corresponding Fab-encoding sequences from anti-RANKL clone IK22-5 20 and anti-PD-1 clone RMP1-14 21 onto an IgG1 backbone.Do anti-RANKL/PD-1 antibodies have superior anti-tumor activity?
An equivalent or superior anti-tumor response was observed with the anti-RANKL/PD-1 BsAb compared with the combination of parental anti-RANKL plus anti-PD-1 antibodies depending upon the tumor model. Mechanistically, the anti-tumor activity of anti-RANKL/PD-1 BsAb required CD8 + T cells, host PD-1 and IFNγ.Does anti-RANKL/PD-1 BSAB block RANKL-dependent osteoclast formation?
The anti-RANKL/PD-1 BsAb retained binding to both RANKL and PD-1 and blocked the interaction with respective counter-structures RANK and PD-L1. The inhibitory effect of anti-RANKL/PD-1 BsAb was confirmed by demonstrating a complete block of RANKL-dependent osteoclast formation.