T Cell-Mediated Targeted Delivery of Anti-PD-L1 Nanobody Overcomes Poor Antibody Penetration and Improves PD-L1 Blocking at the Tumor Site.

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.

Apoptosis of tumor-infiltrating T lymphocytes: a new immune checkpoint mechanism.

Immunotherapy based on checkpoint inhibitors is providing substantial clinical benefit, but only to a minority of cancer patients. The current priority is to understand why the majority of patients fail to respond. Besides T-cell dysfunction, T-cell apoptosis was reported in several recent studies as a relevant mechanism of tumoral immune resistance.