Search Results (10)

Rose Bengal (RB) is an anionic xanthene dye with multiple useful biological features, including photosensitization properties. RB was studied extensively as a photosensitizer, mostly for antibacterial and antitumor photodynamic therapy (PDT). The application of RB to virus inactivation is rather understudied, and no RB derivatives have been developed as antivirals. In this work, we used a synthetic approach based on a successful design of photosensitizing antivirals to produce RB derivatives for virus photoinactivation. A series of n-alkyl-substituted RB derivatives was synthesized and evaluated as antiviral photosensitizers. The compounds exhibited similar ¹O₂ generation rate and efficiency, but drastically different activities against SARS-CoV-2, CHIKV, and HIV; with comparable cytotoxicity for different cell lines. Submicromolar-to-subnanomolar activities and high selectivity indices were detected for compounds with C_4-6 alkyl (SARS-CoV-2) and C_6-8 alkyl (CHIKV) chains. Spectrophotometric assessment demonstrates low aqueous solubility for C_8-10 congeners and a significant aggregation tendency for the C₁₂ derivative, possibly influencing its antiviral efficacy. Initial evaluation of the synthesized compounds makes them promising for further study as viral inactivators for vaccine preparations. Full article

Therapeutic cancer vaccines have become firmly established as a reliable and proficient form of tumor immunotherapy. They represent a promising approach for substantial advancements in the successful treatment of malignant diseases. One attractive vaccine strategy is using, as the vaccine material, the whole tumor cells treated ex vivo by rapid tumor ablation therapies that instigate stress signaling responses culminating in immunogenic cell death (ICD). One such treatment is photodynamic therapy (PDT). The underlying mechanisms and critical elements responsible for the potency of these vaccines are discussed in this review. Radiotherapy has emerged as a suitable component for the combined therapy protocols with the vaccines. Arguments and prospects for optimizing tumor control using a radiovaccination strategy involving X-ray irradiation plus PDT vaccines are presented, together with the findings supporting its validity. Full article

Light and lasers, as high-tech devices whose medical potential has yet to be fully discovered, have made important contributions to medicine, even in the current pandemic. The main aim of this review was to investigate how light was applied as a therapeutic tool during a crisis triggered by COVID-19. Another goal was to encourage scientists and industry to quickly design new at-home photobiomodulation therapy (PBMT) and/or antimicrobial photodynamic therapy (aPDT) easy to use systems to end this pandemic, especially for those who believe in high-tech but would never get vaccinated. This review revealed that PBMT has been successfully applied as adjunct therapy, in combination with conventional medical treatment, and as a pioneering action in SARS-CoV-2 infection, demonstrating significant improvements in airway inflammation and general clinical condition of patients, a faster recovery, avoiding intensive care unit (ICU) hospitalization, mechanical ventilation, mortality, and overcoming long-term sequelae. Application in only a limited number of cases strongly suggests the need for future randomized, placebo-controlled clinical trials to objectively determine the action and effects of PBMT in COVID-19. Implementation of unparalleled theragnostics methods and light-based techniques for disinfection of spaces, air, skin, mucosae, and textures to decrease the load of SARS-CoV-2 virus would save lives, time, and money. In this ongoing and challenging search for the seemingly intangible end of this pandemic, a non-invasive, easily accessible, safe, and side-effect-free adjuvant method appears to be PBMT, alone or in synergistic combination with aPDT, which has been shown to work in COVID-19 and opens unprecedented potential for use as home self-treatment to end the pandemic. Full article

Purpose: Bladder cancer is the 13th most common cause of cancer death with the highest lifetime cost for treatment of all cancers. This scoping review clarifies the available evidence on the role of a novel therapeutic approach called immunogenic cell death (ICD) in urothelial cancer of the bladder. Methods: In accordance with the recommendations of the Joanna Briggs Institute, we searched MEDLINE (Ovid), EMBASE, CENTRAL databases, and supplemented with manual searches through the conferences, Google scholar, and clinicaltrials.gov for published studies up to April 2022. We included literature that studied molecular mechanisms of ICD and the role of certain danger-associated molecular patterns (DAMPs) in generating ICD, safety and efficacy of different ICD inducers, and their contributions in combination with other urothelial cancer treatments. Results: Oncolytic viruses, radiotherapy, certain chemo/chemo radiation therapy combinations, photodynamic therapy, and novel agents were studied as ICD-inducing treatment modalities in the included studies. ICD was observed in vitro (murine or human urothelial carcinoma) in ten studies, eight studies were performed on mouse models (orthotopic or subcutaneous), and five clinical trials assessed patient response to ICD inducing agents. The most common studied DAMPs were Calreticulin, HMGB1, ATP, and Heat Shock Proteins (HSP) 70 and 90, which were either expressed on the cancer cells or released. Conclusion: ICD inducers were able to generate lasting antitumor immune responses with memory formation in animal studies (vaccination effect). In clinical trials these agents generally had low side effects, except for one trial, and could be used alone or in combination with other cancer treatment strategies in urothelial cancer patients. Full article

Photodynamic therapy (PDT)-based cancer vaccines are shown to be more effective modalities for treating cancer in animal models compared to other methods used to generate cancer cell-derived vaccines. The higher efficacy seems to stem from the generation of cell membrane nanovesicles or fragments that carry both cancer cell-specific antigens and high surface content of damage-associated molecular pattern (DAMP) molecules induced by oxidative stress. To develop more effective cancer vaccines in this direction, we explored the generation of cancer vaccines by applying different sources of oxidative stress on cancer cell cultures followed by spontaneous release or filter extrusions to produce cancer cell-derived DAMP-expressing nanovesicles. Through an in-vitro test based on the co-culture of cancer cells and macrophages, it was found that the nanovesicle vaccines generated by H${}_2$O${}_2$ are as effective as those generated by PDT in diminishing cancer cell culture masses, providing a simpler way to manufacture vaccines. In addition, the nanovesicle vaccines produced by filter extrusion are as potent as those produced by spontaneous release, rendering a more stable way for vaccine production. Full article

Photodynamic therapy (PDT), which combines light and oxygen with a photosensitizer to induce reactive oxygen species (ROS)-mediated killing of primary tumor cells, benefits from non-invasive properties and its negligible toxicity to surrounding healthy tissues. In this study, we have shown that the second-generation photosensitizer FOSCAN can be internalized by tumor cells and effectively induce tumor cell death when exposed to laser irradiation in vitro. In addition, these dying tumor cells can be phagocytosed by dendritic cells and lead to their activation and maturation as assessed by in vitro co-culture models. While PDT induces immunogenic tumor cell apoptosis, its application for the treatment of tumors located in deep tissues and advanced malignancies has been limited. In this study, we demonstrate that hepatitis B core virus-like particles (HBc VLPs) can serve as a vaccine to enhance PDT-induced anti-cancer immunity by priming humoral immune responses and inducing CD8⁺ T cell responses. The combination of PDT and HBc VLPs increased the survival rate of MC-38 tumor-bearing mice to 55%, compared to 33% in PDT alone and no tumor-free mice in vaccine alone. Moreover, the combination effectively prevented tumor recurrence in vivo through enhanced immune memory T cells after therapy. Therefore, as both are clinically approved techniques, this combination provides a promising strategy for cancer therapy. Full article

The principal event in the function of whole-cell cancer vaccines is the ingestion of vaccine-delivered tumor antigen-containing material, which is performed by the patient’s antigen-presenting cells (APCs) through the employment of their phagocytic receptors. The goal of the present study was to identify the phagocytic receptors critical for the therapeutic efficacy of whole-cell cancer vaccines. The model of photodynamic therapy (PDT)-generated vaccines based on mouse SCCVII tumors was utilized, with in vitro expanded SCCVII cells treated by PDT serving as the vaccine material used for treating mice bearing established SCCVII tumors. The therapeutic impact, monitored as delayed progression of vaccinated tumors, was almost completely eliminated when antibodies specifically blocking the activity of LOX-1 scavenger receptor were administered to mice 30 min before vaccination. Similar, but much less pronounced, impacts were found with antibodies neutralizing the activity of CR3/CR4 receptors recognizing complement-opsonized vaccine cells, and with those blocking activating Fcγ receptors that recognized IgG antibody-based opsonins. A strikingly contrary action, a greatly enhanced tumor control by the vaccine, was found by blocking immune inhibitory receptor, FcγRIIB. The reported findings establish, therefore, an attractive strategy that can be effectively exploited for potent therapeutic enhancement of PDT-generated (and probably other) whole-cell tumor vaccines. Full article

The potential of dendritic cell (DC)-based immunotherapy to treat cancer is, nowadays, well documented. Still, the clinical success of immune checkpoint inhibitors has dampened the interest in anticancer DC vaccination. For highly life-threatening tumors that are regarded as nonimmunogenic, such as mesothelioma, however, T helper 1 immunity-biased DC-based immunotherapy could still represent an attractive strategy. In this study, we took advantage of photodynamic therapy (PDT) to induce immunogenic cell death to generate mesothelioma cell lysates for DC priming and evaluated such a vaccine to treat peritoneal mesothelioma. We found that the white light in vitro activation of the photosensitizer OR141 led to mesothelioma cell death, together with the release of bona fide danger signals that promote DC maturation. The administration of a PDT-based DC vaccine to mice bearing peritoneal mesothelioma led to highly significant survival when compared with sham or control animals treated with anti-CTLA4 antibodies. This was further supported by a strong CD8⁺ and CD4⁺ T cell response, characterized by an increased proliferation, cytotoxic activities and the expression of activation markers, including interferon gamma (IFNγ). Moreover, the PDT-based DC vaccine led to a significant increase in IFNγ⁺ T cells infiltered within mesothelioma, as determined by flow cytometry and immunohistochemistry. Finally, in vivo tracking of intraperitoneally administered DCs led us to document rapid chemotaxis towards tumor-occupied lymphatics (vs. lipopolysaccharide (LPS)-treated DC). DCs pulsed with PDT-killed mesothelioma cells also exhibited a significant increase in CCR7 receptors, together with an intrinsic capacity to migrate towards the lymph nodes. Altogether, these results indicate that PDT-based DC vaccination is particularly suited to induce a potent immune response against peritoneal mesothelioma. Full article

Myeloid regulatory cells (Mregs) are, together with regulatory T cells (Tregs), a dominant effector population responsible for restriction of the duration and strength of antitumor immune response. Photodynamic therapy (PDT) and cancer vaccines generated by PDT are modalities whose effectiveness in tumor destruction is closely dependent on the associated antitumor immune response. The present study investigated whether the immunodepletion of granulocytic Mregs in host mice by anti-GR1 antibody would improve the response of tumors to PDT or PDT vaccines in these animals. Anti-GR1 administration immediately after Temoporfin-PDT of mouse SCCVII tumors abrogated curative effect of PDT. The opposite effect, increasing PDT-mediated tumor cure-rates was attained by delaying anti-GR1 treatment to 1 h post PDT. With PDT vaccines, multiple anti-GR1 administrations (days 0, 4, and 8 post vaccination) improved the therapy response with SCCVII tumors. The results with PDT suggest that neutrophils (boosting antitumor effect of this therapy) that are engaged immediately after photodynamic light treatment are within one hour replaced with a different myeloid population, presumably Mregs that hampers the therapy-mediated antitumor effect. Anti-GR1 antibody, when used with optimal timing, can improve the efficacy of both PDT of tumors in situ and PDT-generated cancer vaccines. Full article

Photodynamic therapy (PDT)-generated cancer vaccine represents an attractive potential application of PDT, therapeutic modality destroying targeted lesions by localized photooxidative stress. Since immunoregulatory cell activity has become recognized as a major obstacle to effective cancer immunotherapy, the present study examined their participation in the therapeutic effect of PDT cancer vaccine. Following protocols from previous studies, mouse with squamous cell carcinoma SCCVII tumors were vaccinated by SCCVII cells treated by PDT and response monitored by tumor size measurement. The effects of low-dose cyclophosphamide (50 mg/kg) and all-trans retinoic acid (ATRA) on the numbers of Tregs and myeloid-derived suppressor cells (MDSCs) were determined by antibody staining followed by flow cytometry, while their impact on PDT vaccine therapy was evaluated by monitoring changes in tumor responses. Cyclophosphamide effectively reduced the numbers of Tregs, which became elevated following PDT vaccine treatment, and this resulted in an increase in the vaccine’s effectiveness. A similar benefit for the therapy outcome with PDT vaccine was attained by ATRA treatment. The activities of Tregs and MDSCs thus have a critical impact on therapy outcome with PDT vaccine and reducing their numbers substantially improves the vaccine’s effectiveness. Full article