Development of bi-functional hybrid IgGA antibodies for enhancing cancer immunotherapy

Bi-functional recombinant hybrid anti-PD-L1-IgGA antibody combines the effector functions of IgG and IgA and is also directed against the ligand of the programmed cell death1 receptor (PD-L1) to enhance cancer immunotherapy. Blocking the PD-1/PD-L1 signaling pathway using anti-PD-L1-IgGA is an effective new therapeutic approach that restores the functions of immune cells to kill cancer with high efficacy. In this study, the developed novel functional and high affinity human recombinant cross-isotype IgGA antibodies to PD-L1 were successfully produced in mammalian expression systems. We demonstrated that anti-PD-L1-IgGA has high specific binding activity to PD-L1 protein. FPIA analysis yielded a Kd of approximately 1.14 nM PD-1/PD-L1 blockade for determining the inhibition activity of anti-PD-L1 antibody was shown by TR-FRET-based blockade assay. Cross-isotype anti-PD-L1-IgGA antibodies may provide a basis for further development in cancer immunotherapy.