1. T Cell-Mediated Targeted Delivery of Anti-PD-L1 Nanobody Overcomes Poor Antibody Penetration and Improves PD-L1 Blocking at the Tumor Site.
- Author
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Petit PF, Bombart R, Desimpel PH, Naulaerts S, Thouvenel L, Collet JF, Van den Eynde BJ, and Zhu J
- Subjects
- Antibodies, Monoclonal pharmacology, Antibodies, Monoclonal therapeutic use, Humans, Immunotherapy, T-Lymphocytes, B7-H1 Antigen, Neoplasms drug therapy
- 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., (©2022 American Association for Cancer Research.)
- Published
- 2022
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