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Proceedings Paper

Understanding the first steps towards immune-modulation triggered by nanobody-targeted photodynamic therapy (Conference Presentation)

Paper Abstract

Nanobody-targeted photodynamic therapy (NB-PDT) has been developed as a potent and more tumor-specific approach compared to conventional PDT [1]. Interestingly, conventional PDT is able to induce immunogenic cell death, characterized by the exposure/release of damage associated molecular patterns (DAMPs) from dying cells, which can result in an anti-tumor immune response. In this study, we aim at understanding the first steps towards immune-modulation triggered by NB-PDT. For this, the EGFR-targeted NB 7D12 was conjugated to the photosensitizer IRDye700DX and used to perform NB-PDT on EGFR-overexpressing A431 tumor cells, exposed to 30 minute incubation with the conjugates and followed by a light dose of 10 J/cm2. The cytoplasmic DAMP HSP70 was detected on the cell membrane after mild NB-PDT (1 nM conjugate), while it was detected in the medium after highly toxic NB-PDT (25 nM conjugate). The nuclear DAMP HMGB1 was found in the cell cytoplasm under both NB-PDT conditions. Furthermore, cells treated with highly toxic NB-PDT showed an increased release of the pro-inflammatory cytokines IL-1β and IL-6, and a decreased release of pro-tumoral IL-8. Lastly, medium collected from tumor cells treated with highly toxic NB-PDT was able to induce the phenotypic maturation of a dendritic cell line, as indicated by the upregulation of CD40, CD86 and MHCII. Altogether, these results are the first to indicate immune-modulation by NB-PDT, which can be exploited to increase NB-PDT efficacy even further.

Paper Details

Date Published: 14 August 2019
Proc. SPIE 11070, 17th International Photodynamic Association World Congress, 110703Q (14 August 2019); doi: 10.1117/12.2526108
Show Author Affiliations
Irati Beltrán Hernández, Utrecht Univ. (Netherlands)
Tommaso Del Buono D'Ondes, Utrecht Univ. (Netherlands)
Alessia Di Maggio, Utrecht Univ. (Netherlands)
Sabrina Oliveira, Utrecht Univ. (Netherlands)

Published in SPIE Proceedings Vol. 11070:
17th International Photodynamic Association World Congress
Tayyaba Hasan, Editor(s)

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