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Cancers
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Innovative Cancer Treatments and Photodynamic Therapy
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Innovative Cancer Treatments and Photodynamic Therapy

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Clinical Research of Cancer".

Deadline for manuscript submissions: closed (5 February 2023) | Viewed by 23451

Special Issue Editor

Prof. Dr. Nadira Delhem

E-Mail Website
Guest Editor
INSERM U1189 (ONCOTHAI Unit), Institut de Biologie de Lille, Universitéde Lille, Institut Pasteur de Lille, F-59021 Lille, France
Interests: immunology; oncolog; immunotherapy; laser photodynamic therapy; regulatory t cells; exosomes; virus-associtated cancers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer remains a leading cause of death in many countries, and treatment of the advanced stages of the disease is still limited. Discoveries and progress in the field of immunotherapy bring the most exciting developments for delivering a potential cure for advanced cancer. However, the resistance mechanisms acquired in immunotherapies require combinations of treatments in order to optimize the effectiveness of anti-tumor immunotherapies or the development of innovative cancer treatments. In this context, understanding many changes in tumor microenvironment and antitumor responses is pivotal for further development of novel and innovative therapeutics, such as Photodynamic Therapy (PDT), Hypofractioned Stereotaxic Radiotherapy (HSR), Oncolytic Virotherapy, or the combination of immunotherapies or PDT with conventional treatments (chemotherapy, radiotherapy, targeted therapy, or surgery, etc.)

Following recent discoveries of connection of PDT with immune response, standard-of-care PDT effects have also been linked to immune cell-mediated anticancer effects.

The aim of this Special Section is to publish findings that relate to innovative cancer treatments and therapies based on photodynamic therapy. Topics include, but are not limited to:

  • checkpoint blockade
  • innate immunity
  • adaptive responses
  • Oncolytic Virotherapy
  • Photodynamic therapy
  • Combination of treatments
  • immune evasion
  • immunosuppression
  • tumor microenvironment
  • PDT combined to conventional treatments

Prof. Dr. Nadira Delhem
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • checkpoint blockade
  • innate immunity
  • adaptive responses
  • Oncolytic Virotherapy
  • Photodynamic therapy
  • Combination of treatments
  • immune evasion
  • immunosuppression
  • tumor microenvironment
  • PDT combined to conventional treatments

Published Papers (9 papers)

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Research

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23 pages, 2460 KiB  
Article
Interstitial Photodynamic Therapy of Glioblastomas: A Long-Term Follow-up Analysis of Survival and Volumetric MRI Data
by Marco Foglar, Maximilian Aumiller, Katja Bochmann, Alexander Buchner, Mohamed El Fahim, Stefanie Quach, Ronald Sroka, Herbert Stepp, Niklas Thon, Robert Forbrig and Adrian Rühm
Cancers 2023, 15(9), 2603; https://doi.org/10.3390/cancers15092603 - 4 May 2023
Cited by 8 | Viewed by 1724
Abstract
Background: The treatment of glioblastomas, the most common primary malignant brain tumors, with a devastating survival perspective, remains a major challenge in medicine. Among the recently explored therapeutic approaches, 5-aminolevulinic acid (5-ALA)-mediated interstitial photodynamic therapy (iPDT) has shown promising results. Methods: A total [...] Read more.
Background: The treatment of glioblastomas, the most common primary malignant brain tumors, with a devastating survival perspective, remains a major challenge in medicine. Among the recently explored therapeutic approaches, 5-aminolevulinic acid (5-ALA)-mediated interstitial photodynamic therapy (iPDT) has shown promising results. Methods: A total of 16 patients suffering from de novo glioblastomas and undergoing iPDT as their primary treatment were retrospectively analyzed regarding survival and the characteristic tissue regions discernible in the MRI data before treatment and during follow-up. These regions were segmented at different stages and were analyzed, especially regarding their relation to survival. Results: In comparison to the reference cohorts treated with other therapies, the iPDT cohort showed a significantly prolonged progression-free survival (PFS) and overall survival (OS). A total of 10 of 16 patients experienced prolonged OS (≥ 24 months). The dominant prognosis-affecting factor was the MGMT promoter methylation status (methylated: median PFS of 35.7 months and median OS of 43.9 months) (unmethylated: median PFS of 8.3 months and median OS of 15.0 months) (combined: median PFS of 16.4 months and median OS of 28.0 months). Several parameters with a known prognostic relevance to survival after standard treatment were not found to be relevant to this iPDT cohort, such as the necrosis–tumor ratio, tumor volume, and posttreatment contrast enhancement. After iPDT, a characteristic structure (iPDT remnant) appeared in the MRI data in the former tumor area. Conclusions: In this study, iPDT showed its potential as a treatment option for glioblastomas, with a large fraction of patients having prolonged OS. Parameters of prognostic relevance could be derived from the patient characteristics and MRI data, but they may partially need to be interpreted differently compared to the standard of care. Full article
(This article belongs to the Special Issue Innovative Cancer Treatments and Photodynamic Therapy)
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19 pages, 10954 KiB  
Article
Precision Killing of M2 Macrophages with Phage-Displayed Peptide-Photosensitizer Conjugates
by Mouldy Sioud and Qindong Zhang
Cancers 2023, 15(7), 2009; https://doi.org/10.3390/cancers15072009 - 28 Mar 2023
Cited by 2 | Viewed by 1921
Abstract
Among the immunosuppressive cells recruited to the tumor microenvironment, macrophages are particularly abundant and involved in angiogenesis, metastasis, and resistance to current cancer therapies. A strategy that simultaneously targets tumor cells and macrophages, particularly pro-tumoral M2 macrophages, would have significant clinical impact for [...] Read more.
Among the immunosuppressive cells recruited to the tumor microenvironment, macrophages are particularly abundant and involved in angiogenesis, metastasis, and resistance to current cancer therapies. A strategy that simultaneously targets tumor cells and macrophages, particularly pro-tumoral M2 macrophages, would have significant clinical impact for various types of solid malignancies. By the use of phage display technology, we have recently developed a synthetic peptide, named NW, which binds to M1 and M2 macrophages with high affinity. Additional affinity selection on M2 macrophages identified only dominant peptides whose binding motifs are similar to that of the NW peptide. To reduce the frequency of selecting such dominating peptides, the peptide library was affinity selected on M2 macrophages blocked with NW peptide. This approach resulted in the selection of peptides that bind to M2, but not M1 macrophages. To explore the therapeutic potential of the selected peptides, the M13 phage-displayed peptides were conjugated to the photosensitizer IR700, which has been used for cancer photoimmunotherapy. The phage displaying a dominant peptide (SPILWLNAPPWA) killed both M1 and M2 macrophages, while those displaying the M2-specific peptides killed M2 macrophages only upon near-infrared light exposure. A significant fraction of the M2 macrophages were also killed with the untargeted M13 phage-IR700 conjugates. Hence, M2 macrophages can also be selectively targeted by the wild type M13 phage, which displayed a significant tropism to these cells. The benefits of this photoimmunotherapy include an automatic self-targeting ability of the wild type M13 phage, and the option of genetic manipulation of the phage genome to include tumor targeting peptides, allowing the killing of both M2 macrophages and cancer cells. Full article
(This article belongs to the Special Issue Innovative Cancer Treatments and Photodynamic Therapy)
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Graphical abstract

13 pages, 3067 KiB  
Article
Correlation of Intraoperative 5-ALA-Induced Fluorescence Intensity and Preoperative 11C-Methionine PET Uptake in Glioma Surgery
by Kazuhide Shimizu, Kaoru Tamura, Shoko Hara, Motoki Inaji, Yoji Tanaka, Daisuke Kobayashi, Takashi Sugawara, Hiroaki Wakimoto, Tadashi Nariai, Kenji Ishii, Ichiro Sakuma and Taketoshi Maehara
Cancers 2022, 14(6), 1449; https://doi.org/10.3390/cancers14061449 - 11 Mar 2022
Cited by 6 | Viewed by 2787
Abstract
Background: 5-Aminolevulinic acid (5-ALA) is widely employed to assist fluorescence-guided surgery for malignant brain tumors. Positron emission tomography with 11C-methionine (MET-PET) represents the activity of brain tumors with precise boundaries but is not readily available. We hypothesized that quantitative 5-ALA-induced fluorescence intensity [...] Read more.
Background: 5-Aminolevulinic acid (5-ALA) is widely employed to assist fluorescence-guided surgery for malignant brain tumors. Positron emission tomography with 11C-methionine (MET-PET) represents the activity of brain tumors with precise boundaries but is not readily available. We hypothesized that quantitative 5-ALA-induced fluorescence intensity might correlate with MET-PET uptake in gliomas. Methods: Adult patients with supratentorial astrocytic gliomas who underwent preoperative MET-PET and surgical tumor resection using 5-ALA were enrolled in this prospective study. The regional tumor uptake of MET-PET was expressed as the ratio of standardized uptake volume max to that of the normal contralateral frontal lobe. A spectrometric fluorescence detection system measured tumor specimens’ ex vivo fluorescence intensity at 635 nm. Ki-67 index and IDH mutation status were assessed by histopathological analysis. Use of an antiepileptic drug (AED) and contrast enhancement pattern on MRI were also investigated. Results: Thirty-two patients, mostly with Glioblastoma IDH wild type (46.9%) and anaplastic astrocytoma IDH mutant (21.9%), were analyzed. When the fluorescence intensity was ranked into four groups, the strongest fluorescence group exhibited the highest mean MET-PET uptake and Ki-67 index values. When rearranged into fluorescence Visible or Non-visible groups, the Visible group had significantly higher MET-PET uptake and Ki-67 index compared to the Non-visible group. Contrast enhancement on MRI and IDH wild type tumors were more frequent among the Visible group. AED use did not correlate with 5-ALA-induced fluorescence intensity. Conclusions: In astrocytic glioma surgery, visible 5-ALA-induced fluorescence correlated with high MET-PET uptake, along with a high Ki-67 index. Full article
(This article belongs to the Special Issue Innovative Cancer Treatments and Photodynamic Therapy)
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15 pages, 3727 KiB  
Article
Phototheranostics of Cervical Neoplasms with Chlorin e6 Photosensitizer
by Aida Gilyadova, Anton Ishchenko, Artem Shiryaev, Polina Alekseeva, Kanamat Efendiev, Radmila Karpova, Maxim Loshchenov, Victor Loschenov and Igor Reshetov
Cancers 2022, 14(1), 211; https://doi.org/10.3390/cancers14010211 - 2 Jan 2022
Cited by 13 | Viewed by 3449
Abstract
(1) Purpose: Improving the treatment effectiveness of intraepithelial neoplasia of the cervix associated with human papillomavirus infection, based on the application of the method of photodynamic therapy with simultaneous laser excitation of fluorescence to clarify the boundaries of cervical neoplasms. (2) Methods: Examination [...] Read more.
(1) Purpose: Improving the treatment effectiveness of intraepithelial neoplasia of the cervix associated with human papillomavirus infection, based on the application of the method of photodynamic therapy with simultaneous laser excitation of fluorescence to clarify the boundaries of cervical neoplasms. (2) Methods: Examination and treatment of 52 patients aged 22 to 53 years with morphologically and cytologically confirmed mild to severe intraepithelial cervix neoplasia, preinvasive, micro-invasive, and squamous cell cervix carcinoma. All patients were carriers of human papillomavirus infection. The patients underwent photodynamic therapy with simultaneous laser excitation of fluorescence. The combined use of video and spectral fluorescence diagnostics for cervical neoplasms made it possible to control the photodynamic therapy process at all stages of the procedure. Evaluation of the photodynamic therapy of intraepithelial cervical neoplasms was carried out with colposcopic examination, cytological conclusion, and morphological verification of the biopsy material after the photodynamic therapy course. The success of human papillomavirus therapy was assessed based on the results of the polymerase chain reaction. (3) Results. The possibility of simultaneous spectral fluorescence diagnostics and photodynamic therapy using a laser source with a wavelength of 660 nm has been established, making it possible to assess the fluorescence index in real-time and control the photobleaching of photosensitizers in the irradiated area. The treatment of all 52 patients was successful after the first photodynamic therapy procedure. According to the PCR test of the discharge from the cervical canal, the previously identified HPV types were not observed in 48 patients. Previously identified HPV types were absent after repeated PDT in four patients (CIN III (n = 2), CIS (n = 2)). In 80.8% of patients, regression of the lesion was noted. (4) Conclusions. The high efficiency of photodynamic therapy with intravenous photosensitizer administration of chlorin e6 has been demonstrated both in relation to eradication therapy of human papillomavirus and in relation to the treatment of intraepithelial lesions of the cervix. Full article
(This article belongs to the Special Issue Innovative Cancer Treatments and Photodynamic Therapy)
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12 pages, 1482 KiB  
Article
Dramatic Reduction of Distant Pancreatic Metastases Using Local Light Activation of Verteporfin with Nab-Paclitaxel
by Michael Pigula, Zhiming Mai, Sriram Anbil, Myung-Gyu Choi, Kenneth Wang, Edward Maytin, Brian Pogue and Tayyaba Hasan
Cancers 2021, 13(22), 5781; https://doi.org/10.3390/cancers13225781 - 18 Nov 2021
Cited by 2 | Viewed by 1964
Abstract
Despite substantial drug development efforts, pancreatic adenocarcinoma (PDAC) remains a difficult disease to treat, and surgical resection is the only potentially curative option. Unfortunately, 80% of patients are ineligible for surgery due to the presence of invasive disease and/or distant metastases at the [...] Read more.
Despite substantial drug development efforts, pancreatic adenocarcinoma (PDAC) remains a difficult disease to treat, and surgical resection is the only potentially curative option. Unfortunately, 80% of patients are ineligible for surgery due to the presence of invasive disease and/or distant metastases at the time of diagnosis. Treatment strategies geared towards reclassifying these patients as surgical candidates by reducing metastatic burden represents the most promising approach to improve long-term survival. We describe a photodynamic therapy (PDT) based approach that, in combination with the first-line chemotherapeutic nab-paclitaxel, effectively addresses distant metastases in three separate orthotopic PDAC models in immunodeficient mice. In addition to effectively controlling local tumor growth, PDT plus nab-paclitaxel primes the tumor to elicit systemic effects and reduce or abrogate metastases. This combination dramatically inhibits (up to 100%) the eventual development of metastases in models of early stage PDAC, and completely eliminates metastasis in 55% of animals with already established distant disease in late-stage models. Our findings suggest that this light activation process initiates local biological and/or physiological changes within the tumor microenvironment that can be leveraged to treat both localized and distant disease, and potentially reclassify patients with previously inoperable disease as surgical candidates. Full article
(This article belongs to the Special Issue Innovative Cancer Treatments and Photodynamic Therapy)
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15 pages, 4092 KiB  
Article
Interstitial Photodynamic Therapy for Glioblastomas: A Standardized Procedure for Clinical Use
by Henri-Arthur Leroy, Gregory Baert, Laura Guerin, Nadira Delhem, Serge Mordon, Nicolas Reyns and Anne-Sophie Vignion-Dewalle
Cancers 2021, 13(22), 5754; https://doi.org/10.3390/cancers13225754 - 17 Nov 2021
Cited by 16 | Viewed by 2695
Abstract
Glioblastomas (GBMs) are high-grade malignancies with a poor prognosis. The current standard of care for GBM is maximal surgical resection followed by radiotherapy and chemotherapy. Despite all these treatments, the overall survival is still limited, with a median of 15 months. For patients [...] Read more.
Glioblastomas (GBMs) are high-grade malignancies with a poor prognosis. The current standard of care for GBM is maximal surgical resection followed by radiotherapy and chemotherapy. Despite all these treatments, the overall survival is still limited, with a median of 15 months. For patients harboring inoperable GBM, due to the anatomical location of the tumor or poor general condition of the patient, the life expectancy is even worse. The challenge of managing GBM is therefore to improve the local control especially for non-surgical patients. Interstitial photodynamic therapy (iPDT) is a minimally invasive treatment relying on the interaction of light, a photosensitizer and oxygen. In the case of brain tumors, iPDT consists of introducing one or several optical fibers in the tumor area, without large craniotomy, to illuminate the photosensitized tumor cells. It induces necrosis and/or apoptosis of the tumor cells, and it can destruct the tumor vasculature and produces an acute inflammatory response that attracts leukocytes. Interstitial PDT has already been applied in the treatment of brain tumors with very promising results. However, no standardized procedure has emerged from previous studies. Herein, we propose a standardized and reproducible workflow for the clinical application of iPDT to GBM. This workflow, which involves intraoperative imaging, a dedicated treatment planning system (TPS) and robotic assistance for the implantation of stereotactic optical fibers, represents a key step in the deployment of iPDT for the treatment of GBM. This end-to-end procedure has been validated on a phantom in real operating room conditions. The thorough description of a fully integrated iPDT workflow is an essential step forward to a clinical trial to evaluate iPDT in the treatment of GBM. Full article
(This article belongs to the Special Issue Innovative Cancer Treatments and Photodynamic Therapy)
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19 pages, 4117 KiB  
Article
A Warp-Knitted Light-Emitting Fabric-Based Device for In Vitro Photodynamic Therapy: Description, Characterization, and Application on Human Cancer Cell Lines
by Elise Thécua, Laurine Ziane, Guillaume Paul Grolez, Alexandre Fagart, Abhishek Kumar, Bertrand Leroux, Gregory Baert, Pascal Deleporte, Maximilien Vermandel, Anne-Sophie Vignion-Dewalle, Nadira Delhem and Serge Mordon
Cancers 2021, 13(16), 4109; https://doi.org/10.3390/cancers13164109 - 15 Aug 2021
Cited by 3 | Viewed by 2485
Abstract
Photodynamic therapy (PDT) appears to be a promising strategy in biomedical applications. However, the complexity of its parameters prevents wide acceptance. This work presents and characterizes a novel optical device based on knitted light-emitting fabrics and dedicated to in vitro PDT involving low [...] Read more.
Photodynamic therapy (PDT) appears to be a promising strategy in biomedical applications. However, the complexity of its parameters prevents wide acceptance. This work presents and characterizes a novel optical device based on knitted light-emitting fabrics and dedicated to in vitro PDT involving low irradiance over a long illumination period. Technical characterization of this device, called CELL-LEF, is performed. A cytotoxic study of 5-ALA-mediated PDT on human cancer cell lines is provided as a proof of concept. The target of delivering an irradiance of 1 mW/cm2 over 750 cm2 is achieved (mean: 0.99 mW/cm2; standard deviation: 0.13 mW/cm2). The device can maintain a stable temperature with the mean thermal distribution of 35.1 °C (min: 30.7 °C; max: 38.4 °C). In vitro outcomes show that 5-ALA PDT using CELL-LEF consistently and effectively induced a decrease in tumor cell viability: Almost all the HepG2 cells died after 80 min of illumination, while less than 60% of U87 cell viability remained. CELL-LEF is suitable for in vitro PDT involving low irradiance over a long illumination period. Full article
(This article belongs to the Special Issue Innovative Cancer Treatments and Photodynamic Therapy)
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Review

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11 pages, 2215 KiB  
Review
Theranostics Using Indocyanine Green Lactosomes
by Masaki Kaibori, Kosuke Matsui and Mikio Hayashi
Cancers 2022, 14(15), 3840; https://doi.org/10.3390/cancers14153840 - 8 Aug 2022
Cited by 5 | Viewed by 1675
Abstract
Lactosomes™ are biocompatible nanoparticles that can be used for cancer tissue imaging and drug delivery. Lactosomes are polymeric micelles formed by the self-assembly of biodegradable amphiphilic block copolymers composed of hydrophilic polysarcosine and hydrophobic poly-L-lactic acid chains. The particle size can be controlled [...] Read more.
Lactosomes™ are biocompatible nanoparticles that can be used for cancer tissue imaging and drug delivery. Lactosomes are polymeric micelles formed by the self-assembly of biodegradable amphiphilic block copolymers composed of hydrophilic polysarcosine and hydrophobic poly-L-lactic acid chains. The particle size can be controlled in the range of 20 to 100 nm. Lactosomes can also be loaded with hydrophobic imaging probes and photosensitizers, such as indocyanine green. Indocyanine green-loaded lactosomes are stable for long-term circulation in the blood, allowing for accumulation in cancer tissues. Such lactosomes function as a photosensitizer, which simultaneously enables fluorescence diagnosis and photodynamic therapy. This review provides an overview of lactosomes with respect to molecular design, accumulation in cancer tissue, and theranostics applications. The use of lactosomes can facilitate the treatment of cancers in unresectable tissues, such as glioblastoma and head and neck cancers, which can lead to improved quality of life for patients with recurrent and unresectable cancers. We conclude by describing some outstanding questions and future directions for cancer theranostics with respect to clinical applications. Full article
(This article belongs to the Special Issue Innovative Cancer Treatments and Photodynamic Therapy)
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16 pages, 3674 KiB  
Review
Could Photodynamic Therapy Be a Promising Therapeutic Modality in Hepatocellular Carcinoma Patients? A Critical Review of Experimental and Clinical Studies
by Abhishek Kumar, Olivier Moralès, Serge Mordon, Nadira Delhem and Emmanuel Boleslawski
Cancers 2021, 13(20), 5176; https://doi.org/10.3390/cancers13205176 - 15 Oct 2021
Cited by 22 | Viewed by 3352
Abstract
Photodynamic Therapy (PDT) relies on local or systemic administration of a light-sensitive dye, called photosensitizer, to accumulate into the target site followed by excitation with light of appropriate wavelength and fluence. This photo-activated molecule reacts with the intracellular oxygen to induce selective cytotoxicity [...] Read more.
Photodynamic Therapy (PDT) relies on local or systemic administration of a light-sensitive dye, called photosensitizer, to accumulate into the target site followed by excitation with light of appropriate wavelength and fluence. This photo-activated molecule reacts with the intracellular oxygen to induce selective cytotoxicity of targeted cells by the generation of reactive oxygen species. Hepatocellular carcinoma (HCC), one of the leading causes of cancer-associated mortality worldwide, has insufficient treatment options available. In this review, we discuss the mechanism and merits of PDT along with its recent developments as an anti-cancerous therapy. We also highlight the application of this novel therapy for diagnosis, visualization, and treatment of HCC. We examine the underlying challenges, some pre-clinical and clinical studies, and possibilities of future studies associated with PDT. Finally, we discuss the mechanism of an active immune response by PDT and thereafter explored the role of PDT in the generation of anti-tumor immune response in the context of HCC, with an emphasis on checkpoint inhibitor-based immunotherapy. The objective of this review is to propose PDT as a plausible adjuvant to existing therapies for HCC, highlighting a feasible combinatorial approach for HCC treatment. Full article
(This article belongs to the Special Issue Innovative Cancer Treatments and Photodynamic Therapy)
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