Dissemin is shutting down on January 1st, 2025

Published in

American Association for Cancer Research, Cancer Immunology Research, 6(10), p. 713-727, 2022

DOI: 10.1158/2326-6066.cir-21-0801

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

This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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Abstract

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.