Abstract Co-targeting PD-1/PD-L1 and TIGIT/CD226 is being pursued to broaden the efficacy of current immunotherapy. Here we demonstrate that a bispecific antibody (BsAb) targeting PD-L1 and TIGIT, HB0036, shows major advantages over the combination of the two parental monoclonal Abs (mAbs). We demonstrated that HB0036 co-engages PD-L1 + tumour cells and TIGIT + T cells, and thereby upregulates CD226 on T cells and induces a greater T-cell proliferative response compared to the combination of the parental antibodies in vitro . In vivo , HB0036 recruits greater amounts of TIGIT antibody in PD-L1 + tumours but not in PD-L1 - tumours, compared with therapy using the two parental antibodies. We also observed improved tumour control and favourable immunological signatures with HB0036 in syngeneic and xenograft tumour models. Collectively, these findings demonstrate that bispecific antibodies targeting PD-L1 and TIGIT offer superior benefits in cancer immunotherapy compared with therapy using the two parental antibodies. Based on these studies, a phase I clinical trial with HB0036 has been initiated in patients with solid tumours ( NCT05417321 ).

Co-engagement of TIGIT+immune cells to PD-L1+tumours by a bispecific antibody potentiates T-cell response and tumour control