The Potential of Nanobody-Targeted Photodynamic Therapy to Trigger Immune Responses.

Irati Beltrán Hernández,Sabrina Oliveira,Mathieu L. Angelier,Tommaso Del Buono D’Ondes,Alessia Di Maggio,Yingxin Yu

doi:10.3390/cancers12040978

Irati Beltrán Hernández, Sabrina Oliveira + Show 4 more

Open Access

https://doi.org/10.3390/cancers12040978

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Journal: Cancers	Publication Date: Apr 15, 2020
Citations: 23	License type: CC BY 4.0

Affiliation: Utrecht University

Abstract

Nanobody-targeted photodynamic therapy (NB-PDT) has been recently developed as a more tumor-selective approach rather than conventional photodynamic therapy (PDT). NB-PDT uses nanobodies that bind to tumor cells with high affinity, to selectively deliver a photosensitizer, i.e., a chemical which becomes cytotoxic when excited with light of a particular wavelength. Conventional PDT has been reported to be able to induce immunogenic cell death, characterized by the exposure/release of damage-associated molecular patterns (DAMPs) from dying cells, which can lead to antitumor immunity. We explored this aspect in the context of NB-PDT, targeting the epidermal growth factor receptor (EGFR), using high and moderate EGFR-expressing cells. Here we report that, after NB-PDT, the cytoplasmic DAMP HSP70 was detected on the cell membrane of tumor cells and the nuclear DAMP HMGB1 was found in the cell cytoplasm. Furthermore, it was shown that NB-PDT induced the release of the DAMPs HSP70 and ATP, as well as the pro- inflammatory cytokines IL- 1β and IL-6. Conditioned medium from high EGFR-expressing tumor cells treated with NB-PDT led to the maturation of human dendritic cells, as indicated by the upregulation of CD86 and MHC II on their cell surface, and the increased release of IL-12p40 and IL-1β. Subsequently, these dendritic cells induced CD4+ T cell proliferation, accompanied by IFNγ release. Altogether, the initial steps reported here point towards the potential of NB-PDT to stimulate the immune system, thus giving this selective-local therapy a systemic reach.

Highlights

Photodynamic therapy (PDT) was first approved in 1993 for the treatment of bladder cancer and, since its use has expanded to many other oncological indications, such as lung, brain, esophagus, skin, and head and neck cancer [1]
Taking into account possible variations in epidermal growth factor receptor (EGFR) expression and in light penetration, the type of cell death induced by Nanobody-targeted photodynamic therapy (NB-photodynamic therapy (PDT)) was investigated after mild (LD50) and highly cytotoxic (LD100) NB-PDT, on high and moderate EGFR-expressing cells, i.e., A431 and scc-U8 cells, respectively
Necrosis was the main cell death mechanism triggered by NB-PDT on A431 cells (Figure 1a)

Summary

Introduction

Photodynamic therapy (PDT) was first approved in 1993 for the treatment of bladder cancer and, since its use has expanded to many other oncological indications, such as lung, brain, esophagus, skin, and head and neck cancer [1] This treatment relies on the action of a photosensitizer (PS), i.e., a light activatable compound that accumulates into cells and becomes cytotoxic when excited with light of a particular wavelength. Damage to the tumor vasculature and the potential to stimulate an antitumor immune response have been reported [2,3,4] This last aspect is of particular interest since a local treatment such as PDT, making use of locally applied light at the tumor site, could develop systemic effects via the activation of the immune system.

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