Targeting dendritic cells with a PD-L1 based bispecific antibody rejuvenates specific anti-tumor T cells

Bispecific T-cell engagers (BiTEs) that preferentially target tumor-associated antigens to engage CD3 signaling have been approved to treat acute B-cell lymphoblastic leukemia. However, their applications in solid tumors have been hampered by short half-life and severe toxicity at therapeutic doses. Whether antigen-specific T cells would be rejuvenated by directing to tumor cells remains unclear. To address this, we designed a bispecific antibody (BsAb) which simultaneously targets CD3 and immune checkpoint PD-L1. Compared with conventional tumor cell targeting BsAb, PD-L1xCD3 generates superior anti-tumor immune responses in vivo. By single-cell sequencing of tumor-infiltrated T cells in different BiTE treatment, we found that PD-L1xCD3 treatment generate unique T cell subsets in the tumor microenvironment which contribute to the increased antitumor efficacy and reduced side effect.