journal contribution
posted on 2023-04-04, 01:22 authored by Pierre-Florent Petit, Raphaële Bombart, Pierre-Hubert Desimpel, Stefan Naulaerts, Laurie Thouvenel, Jean-François Collet, Benoit J. Van den Eynde, Jingjing Zhu Supplementary Figure from T Cell–Mediated Targeted Delivery of Anti–PD-L1 Nanobody Overcomes Poor Antibody Penetration and Improves PD-L1 Blocking at the Tumor Site
Funding
Le Fonds de la Recherche Fondamentale Stratégique–WELBIO
Fonds pour la Recherche Scientifique
Fondation contre le Cancer
European Union’s Horizon 2020 Research and Innovation Programme
FNRS-aspirant
FRIA
Televie
FNRS-EOS DECODE
Fondation Contre le Cancer
History
ARTICLE 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.
