The impact of photodynamic therapy therapy with polarity-tunable bacteriochlorins on the antitumor immunity: local effects and systemic consequences (Conference Presentation)

Janusz Dabrowski; Barbara Pucelik; Luis G. Arnaut

doi:10.1117/12.2526642

14 August 2019 The impact of photodynamic therapy therapy with polarity-tunable bacteriochlorins on the antitumor immunity: local effects and systemic consequences (Conference Presentation)

Janusz Dabrowski, Barbara Pucelik, Luis G. Arnaut

Author Affiliations +

Proceedings Volume 11070, 17th International Photodynamic Association World Congress; 1107061 (2019) https://doi.org/10.1117/12.2526642
Event: 17th International Photodynamic Association World Congress, 2019, Cambridge, Massachusetts, United States

Abstract

The main goal of this study is to analyze photochemical and molecular mechanisms of PDT with the set of polarity-tunable bacteriochlorins. The relationship of the structure and biological activity of the tested bacteriochlorins (F2BOH, F2BMet, F2BPrc, Cl2BHep) was determined, including (i) physicochemical, spectroscopic and photophysical characterization; (ii) the analysis of in vitro activity (cytotoxicity, subcellular localization, cell death modes); and (iii) the photodynamic efficacy in vivo (vascular versus cellular targeting). A detailed analysis of PDT-induced inflammation and a full characterization of molecular mechanisms were performed. The differences in the efficacy of the chosen phototherapeutic protocols (V-PDT, E-PDT, C-PDT) with optimized PDT conditions (Ps formulation, DLI, light dose) are demonstrated. To elucidate these differences, a Luminex technology was applied to detect a number of cytokines in the tumor and in plasma of PDT-treated mice. Among a wide range of cytokines (IL-6, IL-10, IL-13, IL-15) and chemokines (KC, MIP1, MIP2) released after PDT, an important role is assigned to IL-6. Moreover, expression of recombinant cytokines such as GM-CSF and TNFα significantly enhance antitumor response, whereas blocking anti-inflammatory cytokines such as IL-10 or VEGF improves the cure rates after PDT. Bacteriochlorin-mediated PDT generates specific immune response capable of inducing immunological memory that enables mice to reject a tumor rechallenge. Moreover, we have demonstrated that PDT activates innate and adaptive immunity that result in the eradication of NIR-irradiated primary tumors and the inhibition of untreated distant tumors by generating a systemic tumor-specific cytotoxic T-cell response.

Conference Presentation

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Janusz Dabrowski, Barbara Pucelik, and Luis G. Arnaut "The impact of photodynamic therapy therapy with polarity-tunable bacteriochlorins on the antitumor immunity: local effects and systemic consequences (Conference Presentation)", Proc. SPIE 11070, 17th International Photodynamic Association World Congress, 1107061 (14 August 2019); https://doi.org/10.1117/12.2526642

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KEYWORDS

Photodynamic therapy

Tumors

Biological research

Molecular mechanisms

Cell death

In vitro testing

In vivo imaging

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