OncoThAI will attend the next International Photodynamic Association world congress in Boston and will present 14 papers introducing the most recent results of the lab.
The International Photodynamic Association World Congress has been bringing together researchers and clinicians in all fields of photodynamic therapy and photodiagnosis since 1986. Every two years, the IPA organizes a conference to foster scientific development and contribute to clinical practice. The 17th IPA World Congress will be held at the Marriott Cambridge, Massachusetts, June 28 - July 4, 2019.
Here is the list of our 14 papers:
DOSINDYGO: DOSe finding for INtraoperative photoDYnamic therapy of GliOblastoma
Paper 11070-194
Author(s): Clément Dupont, Fabienne Lecomte, Pascal Deleporte, Gregory Baert, Serge R. Mordon, Nicolas Reyns, Maximilien Vermandel, OncoThAI INSERM (France)
Glioblastoma is a malignant brain tumor with a poor prognosis. Currently, complete resection is rarely feasible, since tumor cells usually infiltrate the surrounding brain. The INDYGO clinical trial has been achieved to assess the toxicity of intraoperative photodynamic therapy to treat newly diagnosed Glioblastoma. Today, we believe that the PDT effect can be improved by a higher light dose. The DOSINDYGO clinical trial aims to achieve a light-dose escalation, increasing up to four times the initial light dose used in the INDYGO trial. These light doses should allow to treat deeper in tissues and thus decrease the recurrence risk.
Impact of photodynamic therapy on the regulation of human immune system in the context of hepatocellular carcinoma
Paper 11070-239
Author(s): Abhishek Kumar, Olivier Morales, Martha Baydoun, Institut de Biologie de Lille (France); Bertrand Leroux, Institut de Biologie de Lille (France), INSERM (France); Elise Thécua, OncoThAI INSERM (France); Lynda Aoudjehane, Institute of Cardiometabolism and Nutrition (France); Alexandre Quilbe, Clémentine de Schutter, Institut de Biologie de Lille (France); Céline Frochot, Lab. Réactions et Génie des Procédés (France); Serge R. Mordon, INSERM (France); Emmanuel Boleslawski, Nadira Delhem, Institut de Biologie de Lille (France)
The high frequency of Hepatocellular Carcinoma (HCC) patients and the unsatisfactory results obtained with conventional treatments, encouraged investigations for alternative treatments such as photodynamic therapy (PDT). In this study, we evaluated the efficacy of 5-Aminolevulinic acid (5-ALA) mediated PDT on HCC and the influence of 5-ALA PDT on human immune system. Our preliminary results demonstrated that PDT can be effective against HCC cell lines, inducing a dose-dependent cell death in a pattern related to the p53 expression profile. Interestingly, conditioned media of PDT-treated HCC cell lines induce a decrease of HCC cell proliferation and an increase of human PBMC proliferation.
Impact of serum exosomes from multifractionated interstitial ALA-PpIX photodynamic therapy treated glioblastoma-rat model on immune cells
Paper 11070-240
Author(s): Olivier Morales, CNRS (France); Mathilde Quidet, Ctr. Hospitalier Regional Univ. de Lille (France); Clément Dupont, OncoThAI INSERM (France); Bertrand Leroux, Univ. de Lille (France), Institut de Biologie de Lille (France), Institut Pasteur de Lille (France); Clémentine de Schutter, Institut de Biologie de Lille (France); Nicoals Reyns, Ctr. Hospitalier Regional Univ. de Lille (France), Univ. Lille (France); Serge R. Mordon, Maximilien Vermandel, Univ. de Lille (France); Nadira Delhem, CNRS (France)
Photodynamic therapy is proposed for glioblastoma mainly for its capacity to kill tumor cells and to potentially induce an immune activation. Our study aimed to evaluate the impact of serum exosomes produced before and after ALA-PpIX-PDT on immune cells. Immunodeficient rats were xenografted with U87 cells and treated with multifractionated light. MRI revealed an elevated diffusion values in the center of the PDT-treated tumor. High exosome levels were detected in rat’s serum after xenograft while a strong decrease were noticed after PDT treatment. Pre-treated exosomes had an immunosuppressive effect on PBMC, while post-treated exosomes induced a sustained immune cell proliferation.
Photodynamic therapy for skin cancers: how to enhance 5-ALA penetration with dissolving microneedles?
Paper 11070-263
Author(s): Mathilde Champeau, OncoThAI INSERM (France), CEA-LETI (France); Séverine Vignoud, CEA-LETI (France); Laurent Mortier, Serge R. Mordon, OncoThAI INSERM (France)
Photodynamic therapy (PDT) induced by protoporphyrin IX (PpIX) has been widely used in treatment of skin cancers. Clearance rate depends on different factors such as light irradiation, skin oxygenation and drug penetration. The penetration of 5-aminolevulinic acid (5-ALA) with topical application is currently limited and restrains the production of PpIX which could restrict PDT outcomes. A microneedle (MN) patch containing 5-ALA has been developed to accelerate drug delivery and enhance PpIX presence in deep skin layers. After an in vivo experiment on hairless rats, MN-patch’s parameters have been optimized in order to obtain maximum PpIX fluorescence.
PDT in dermatology: quantification, relevance and comparison of light sources within a few clicks
Paper 11070-268
Author(s): Anne-Sophie Vignion-Dewalle, Gregory Baert, Elise Thecua, Fabienne Lecomte, OncoThAI INSERM (France); Claire Vicentini, OncoThAI INSERM (France), Ctr. Hospitalier Regional Univ. de Lille (France); Laurent Mortier, OncoThAI INSERM (France), Ctr. Hospitalier Regional Univ. de Lille (France); Serge R. Mordon, OncoThAI INSERM (France)
In dermatology, photodynamic therapy (PDT) relies on the photo-activation of the photosensitizer protoporphyrin IX (PpIX). We have previously developed a freely available website (http://www.oncothai.fr/light-efficiency-calculator/), which computes the PpIX-weighted irradiance of any uploaded spectral irradiance. Resulting from the weighting of this spectral irradiance by the normalized PpIX absorption spectrum, the PpIX-weighted irradiance allows to quantify the efficiency of the corresponding light source in photoactivating PpIX. Through this website, we have assessed a variety of light sources proposed for use in dermatological PDT and obtained a wide range of PpIX-weighted irradiances with a maximum value for daylight on a clear sunny day.
INDYGO: intraoperative PDT for newly diagnosed GBM, 2-years follow-up
Paper 11070-180
Author(s): Maximilien Vermandel, Clément Dupont, Fabienne Lecomte, Pascal Deleporte, Serge R. Mordon, Nicolas Reyns, OncoThAI INSERM (France)
Glioblastoma is a malignant brain tumor with a median overall survival of approximately 15 months with the current standard of care and for which adjuvant therapies are highly expected. 5-ALA PDT have been reported with promising results to treat glioblastoma. We present here a clinical trial to evaluate 5-ALA PDT delivered intraoperatively to treat newly diagnosed GBM. Ten patients have been enrolled. Currently, therapy has been delivered without significant toxicity or adverse event and are fulfilling the primary endpoint of this feasibility study. Secondary endpoints still being under investigation are progression-free survival, overall survival and patients' quality of life.
Treatment of peritoneal carcinomatosis of various origins by photodynamic therapy: state of the art (Invited Paper)
Paper 11070-52
Author(s): Henri Azaïs, Pitié-Salpêtrière Hospital (France), OncoThAI INSERM (France); Martha Baydoun, Christie Rebahi, Olivier Moralès, Institut de Biologie de Lille (France); Céline Frochot, Ludovic Colombeau, Lab. Réactions et Génie des Procédés (France); Bertrand Leroux, Elise Thécua, OncoThAI INSERM (France); Nadira Delhem, CNRS (France); Pierre Collinet, Hôpital Jeanne de Flandre (France), OncoThAI INSERM (France); Serge R. Mordon, OncoThAI INSERM (France)
Surgical management of peritoneal metastases raises the problem of the theoretical involvement of the entire peritoneum. Intraperitoneal photodynamic therapy (PDT) has been limited by the lack of specificity of photosensitizers and difficulties to bring light into the cavity. Recent data may give a new breath for PDT. Indeed, targeted molecules are being developed, and optimization of illumination systems allows the development of PDT by minimally-invasive approaches. Expected abscopal effect of PDT could enhance a systemic immune response. The objective of this review is to present the most recent data and possible approaches for the treatment of peritoneal carcinomatosis by PDT.
Intraperitoneal photodynamic therapy for ovarian cancer: a novel way to stimulate anti-tumoral immune response?
Paper 11070-54
Author(s): Martha Baydoun, Olivier Morales, Institut de Biologie de Lille (France); Céline Frochot, Ludovic Colombeau, Lab. Réactions et Génie des Procédés (France); Bertrand Leroux, Elise Thécua, Laurine Ziane, OncoThAI INSERM (France); Clémentine de Schutter, Institut de Biologie de Lille (France); Pierre Collinet, OncoThAI INSERM (France), CHU Lille (France); Serge R. Mordon, OncoThAI INSERM (France); Henri Azais, OncoThAI INSERM (France), Pitié-Salpêtrière Hospital (France); Nadira Delhem, Institut de Biologie de Lille (France)
Ovarian cancer is the most lethal gynecological cancer in women. In this study, we evaluated both in vitro and in vivo the effect of a new photosensitizer (PS2) on ovarian peritoneal ovarian cancer. We showed that, in vitro and upon 1h of illumination, the PS2-PDT was capable of inducing ovarian cancer cell death and activate the mitochondrial metabolism of some immune cells. Furthermore we developed a mouse model of ovarian cancer stably expressing luciferase in OVCAR-3 cell-line allowing us to follow tumor development. The PS2 was well tolerated by mice and our preliminary results showed a tumor regression upon illumination.
Updated results of a feasibility trial assessing intrapleural photodynamic therapy combined with pleurectomy/decortication then chemotherapy in malignant pleural mesothelioma patients
Paper 11070-68
Author(s): Serge R. Mordon, INSERM (France)
The iPDT multimodal treatment for MPM is applicable and manageable in a European expert center, involving local skills and dedicated teams. The safety profile of the iPDT in Lille center was favorable, as validated by an external board. Median overall survival was promising (≈28 months), similar to previous US results. Our center is expected to join soon a large phase II randomized, multicentric US trial assessing MPM multimodal treatment (P/D, chemotherapy) ±iPDT (NCT02153229; UPENN, USA).
Photodynamic therapy for actinic keratosis: a trend towards a decrease in irradiance without loss of efficacy for a better tolerability
Paper 11070-82
Author(s): Anne-Sophie Vignion-Dewalle, OncoThAI INSERM (France); Claire Vicentini, OncoThAI INSERM (France), Ctr. Hospitalier Regional Univ. de Lille (France); Gregory Baert, Elise Thecua, Fabienne Lecomte, OncoThAI INSERM (France); Laurent Mortier, OncoThAI INSERM (France), Ctr. Hospitalier Regional Univ. de Lille (France); Serge R. Mordon, OncoThAI INSERM (France)
The EU-approved protocols for photodynamic therapy of actinic keratosis require photoactivation with either red-light or daylight. Due to high irradiances, standard red-light photoactivation is painful. Several clinical studies have reported similar efficacy and better tolerability for red-light photoactivation at increasingly lower irradiances compared to standard red-light photoactivation. We have compared the irradiances measured during photoactivation with the Aktilite CL 128 (Galderma SA, Switzerland) with the associated complete responses at 3 months. The comparison purpose was to determine whether there is a minimum irradiance threshold for an effective red-light photoactivation. From this comparison, no such minimum irradiance threshold could be found.
Light emitting fabrics for photodynamic treatment of vulvar primary extramammary Paget's disease
Paper 11070-101
Author(s): Elise Thecua, OncoThAI INSERM (France), MDB Texinov S.A.S. (France); Fabienne Lecomte, Laurine Ziane, Anne-Sophie Vignion-Dewalle, OncoThAI INSERM (France); Cyril Maire, Claire Vicentini, Henry Abirached, OncoThAI INSERM (France), CHU Lille (France); Delphine Staumont, Ctr. Hospitalier Regional Univ. de Lille (France); Laurent Mortier, OncoThAI INSERM (France), Ctr. Hospitalier Regional Univ. de Lille (France); Serge R. Mordon, OncoThAI INSERM (France)
Vulvar primary Extramammary Paget’s disease (EMPD) is a rare intraepithelial adeno-carcinoma. It can progress into an invasive tumor and widely affect patient’s quality of life. Surgery is the mainstay of treatment, but recurrences are common and multiple resections lead to severe functional alterations. Photodynamic therapy (PDT) could be an alternative conservative treatment. To address pain and provide a homogeneous illumination over vulvar and perianal areas, the PAGETEX® device based on light emitting fabrics has been developed. PAGETEX® device is being assessed in clinical study (NCT03713203) which aim to establish the lesion response rate of vulvar EMPD, 3 months after PDT with PAGETEX®, and the tolerability of the treatment.
The role of medical imaging in the context of photodynamic therapy
Paper 11070-144
Author(s): Maximilien Vermandel, Serge R. Mordon, Clément Dupont, OncoThAI INSERM (France)
Photodynamic therapy (PDT) is a modality with promising results for the treatment of various cancers. PDT is increasingly included in the standard of care for different pathologies. This therapy relies on the effects of light delivered to photosensitized cells. The role of medical imaging in this context is crucial to better understand how and where to deliver the therapy but also to observe effects on tumors in post-treatment. At different stages of delivery, PDT requires imaging to plan, evaluate and monitor treatment. The contribution of medical imaging modalities in this context is important and continues to increase.
Light emitting fabrics for PDT: technology and results of clinical studies (Invited Paper)
Paper 11070-175
Author(s): Serge R. Mordon, Anne-Sophie Vignion-Dewalle, Fabienne Lecomte, Pascal Deleporte, Gregory Baert, Elise Thecua, Laurine Ziane, Claire Vicentini, Cyril Maire, Laurent Mortier, OncoThAI INSERM (France)
A homogeneous and reproducible fluence rate delivery during clinical PDT plays a determinant role in preventing under- or overtreatment. The integration of plastic optical fibers into textile structures by knitting can fulfill this requirement. Mean irradiance of 2.5 mW.cm-².W-1 , large emitting area (300 cm²) can be easily achieved. Temperature elevation stays below 1°C for a 45 minutes illumination. These Light Emitting fabrics (LEF) can be connected to any diode laser: 405 nm, 635 nm, 655 nm, etc… LEF were evaluated with success in Dermatology for the treatment of Actinic Keratosis (ClinicalTrials.gov Identifier: NCT03076918 & NCT03076892).
Devices based on light emitting fabrics dedicated to pdt preclinical studies
Paper 11070-179
Author(s): Elise Thecua, Laurine Ziane, Gregory Baert, Pascal Deleporte, Bertrand Leroux, OncoThAI INSERM (France); Abhishek Kumar, Martha Baydoun, Olivier Moralès, Nadira Delhem, Institut de Biologie de Lille (France); Serge R. Mordon, OncoThAI INSERM (France)
Light distribution plays a determinant role in the reproducibility of results of PDT studies. Few illumination devices dedicated to preclinical studies are available and most research teams use home-made solutions that may not always be reproducible. To address these issues, we developed illumination devices dedicated to our preclinical studies, which embed knitted light emitting fabrics (LEF) technology. We designed light plates for aside illumination of 96-cells plates, and mice boxes for homogeneous extracorporeal illumination. Both systems can deliver homogeneous light with an irradiance that can reach several mW/cm2, with varying durations and wavelengths. First results of preclinical studies demonstrate a high reproducibility, with an easy setup, and a great adaptability of illumination modalities.
More information regarding the congress and the program.
