Search

Photodynamic therapy (PDT) with redaporfin stimulates colon carcinoma (CT26), breast (4T1) and melanoma (B16F10) cells to display high levels of CD80 molecules on their surfaces. CD80 overexpression amplifies immunogenicity because it increases same cell (cis) CD80:PD-L1 interactions, which (i) disrupt binding of T-cells PD-1 inhibitory receptors with their ligands (PD-L1) in tumour cells, and (ii) inhibit CTLA-4 inhibitory receptors binding to CD80 in tumour cells. In some cancer cells, redaporfin-PDT also increases CTLA-4 and PD-L1 expressions and virtuous combinations between PDT and immune-checkpoint blockers (ICB) depend on CD80/PD-L1 or CD80/CTLA-4 tumour overexpression ratios post-PDT. This was confirmed using anti-CTLA-4 + PDT combinations to increase survival of mice bearing CT26 tumours, and to regress lung metastases observed with bioluminescence in mice with orthotopic 4T1 tumours. However, the primary 4T1 responded poorly to treatments. Photoacoustic imaging revealed low infiltration of redaporfin in the tumour. Priming the primary tumour with high-intensity (~ 60 bar) photoacoustic waves generated with nanosecond-pulsed lasers and light-to-pressure transducers improved the response of 4T1 tumours to PDT. Penetration-resistant tumours require a combination of approaches to respond to treatments: tumour priming to facilitate drug infiltration, PDT for a strong local effect and a change in immunogenicity, and immunotherapy for a systemic effect., (© 2023. The Author(s).)

Photodynamic therapy (PDT) remains an underutilized treatment modality in oncology. Many efforts have been dedicated to the development of better photosensitizers, better formulations and delivery methods, rigorous planning of light dose distribution in tissues, mechanistic insight, improvement of treatment protocols and combinations with other therapeutic agents. Hopefully, progress in all these fields will eventually expand the use of PDT. Here we offer a brief review of our own contribution to the development of a photosensitizer for PDT - redaporfin - currently in Phase II clinical trials, and present data on its combination with two glycolysis inhibitors: 2-deoxyglucose and 3-bromopyruvate. We show that 3-bromopyruvate is more cytotoxic to a carcinoma cell line (CT26) than to a normal fibroblast (3T3) cell line, and that this selectivity is maintained in the in vitro combination with redaporfin-PDT. This combination was investigated in BALB/c mice with large subcutaneous CT26 tumors and it is shown that the cure rate in the combination is higher (33% cures) than in PDT (11% cures) or in 3-bromopyruvate (no cures) alone. The combination of redaporfin-PDT with 3-bromopyruvate illustrates the potential of combination therapies and how PDT benefits can be enhanced by systemic drugs with complementary targets., (© 2022 The American Society for Photobiology.)

Predicting the extent of necrosis in photodynamic therapy (PDT) is critical to ensure that the whole tumor is treated but vital structures, such as major blood vessels in the vicinity of the tumor, are spared. The models developed for clinical planning rely on empirical parameters that change with the nature of the photosensitizer and the target tissue. This work presents an in vivo study of the necrosis in the livers of rats due to PDT with a bacteriochlorin photosensitizer named redaporfin using both frontal illumination and interstitial illumination. Various doses of light at 750 nm were delivered 15 min postintravenous administration of redaporfin. Sharp boundaries between necrotic and healthy tissues were found. Frontal illumination allowed for the determination of the photodynamic threshold dose-1.5 × 10 19  photons cm -3 -which means that the regions of the tissues exposed to more than 11 mm of ROS evolved to necrosis. Interstitial illumination produced a necrotic radius of 0.7 cm for a light dose of 100 J cm -1 and a redaporfin dose of 0.75 mg kg -1 . The experimental data obtained can be used to inform and improve clinical planning with frontal and interstitial illumination protocols., (© 2020 American Society for Photobiology.)