American Association for Cancer Research, Cancer Immunology Research, 6(10), p. 713-727, 2022
DOI: 10.1158/2326-6066.cir-21-0801
Full text: Unavailable
Abstract Monoclonal antibodies (mAbs) blocking immune checkpoints such as programmed death ligand 1 (PD-L1) have yielded strong clinical benefits in many cancer types. Still, the current limitations are the lack of clinical response in a majority of patients and the development of immune-related adverse events in some. As an alternative to PD-L1–specific antibody injection, we have developed an approach based on the engineering of tumor-targeting T cells to deliver intratumorally an anti–PD-L1 nanobody. In the MC38-OVA model, our strategy enhanced tumor control as compared with injection of PD-L1–specific antibody combined with adoptive transfer of tumor-targeting T cells. As a possible explanation for this, we demonstrated that PD-L1–specific antibody massively occupied PD-L1 in the periphery but failed to penetrate to PD-L1–expressing cells at the tumor site. In sharp contrast, locally delivered anti–PD-L1 nanobody improved PD-L1 blocking at the tumor site while avoiding systemic exposure. Our approach appears promising to overcome the limitations of immunotherapy based on PD-L1–specific antibodies.