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Photodynamic therapy immunotherapy

Kuangda Lu, Chunbai He, Nining Guo, Christina Chan, Kaiyuan Ni, Ralph R Weichselbaum, Wenbin Lin
Photodynamic therapy (PDT) can destroy local tumors and minimize normal tissue damage, but is ineffective at eliminating metastases. Checkpoint blockade immunotherapy has enjoyed recent success in the clinic, but only elicits limited rates of systemic antitumor response for most cancers due to insufficient activation of the host immune system. Here we describe a treatment strategy that combines PDT by a new chlorin-based nanoscale metal-organic framework (nMOF), TBC-Hf, and a small-molecule immunotherapy agent that inhibits indoleamine 2,3-dioxygenase (IDO), encapsulated in the nMOF channels to induce systemic antitumor immunity...
September 28, 2016: Journal of the American Chemical Society
Athanasios Petrou, Demetrios Moris, Patrick Paul Tabet, Brian David Wensley Richards, Georgios Kourounis
Pancreatic ductal adenocarcinoma is a lethal and late presenting malignancy with dismal survival rates. An estimated total of 330,000 people died from this malignancy in 2012. Although there have been improvements in diagnostic and treatment methods, the survival of late stage pancreatic cancer has not shown significant improvement in the past 4 decades. Multiple treatment approaches are available including chemotherapy, radiotherapy, and immunotherapy, but to this day surgical resection remains the only curative treatment option...
May 2016: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Chunbai He, Xiaopin Duan, Nining Guo, Christina Chan, Christopher Poon, Ralph R Weichselbaum, Wenbin Lin
Advanced colorectal cancer is one of the deadliest cancers, with a 5-year survival rate of only 12% for patients with the metastatic disease. Checkpoint inhibitors, such as the antibodies inhibiting the PD-1/PD-L1 axis, are among the most promising immunotherapies for patients with advanced colon cancer, but their durable response rate remains low. We herein report the use of immunogenic nanoparticles to augment the antitumour efficacy of PD-L1 antibody-mediated cancer immunotherapy. Nanoscale coordination polymer (NCP) core-shell nanoparticles carry oxaliplatin in the core and the photosensitizer pyropheophorbide-lipid conjugate (pyrolipid) in the shell (NCP@pyrolipid) for effective chemotherapy and photodynamic therapy (PDT)...
2016: Nature Communications
Dangge Wang, Tingting Wang, Jianping Liu, Haijun Yu, Shi Jiao, Bing Feng, Fangyuan Zhou, Yuanlei Fu, Qi Yin, Pengcheng Zhang, Zhiwen Zhang, Zhaocai Zhou, Yaping Li
Photodynamic therapy (PDT) has emerged as a promising clinical modality for cancer therapy due to its ability to initiate an antitumor immune response. However, PDT-mediated cancer immunotherapy is severely impaired by tumor-cell immunosuppression of host T cell antitumor activity through the programmed cell death 1 ligand (PD-L1) and programmed cell death receptor 1 (PD-1) (PD-L1-PD-1) immune checkpoint pathway. Here, we demonstrate that PDT-mediated cancer immunotherapy can be augmented by PD-L1 knockdown (KD) in tumor cells...
September 14, 2016: Nano Letters
Jie Ji, Yunfeng Zhang, Wei R Chen, Xiuli Wang
Dendritic cell (DC) vaccines were generated by apoptotic squamous cell carcinoma (SCC) cells induced by 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT). ALA-PDT-DC vaccine inhibited the growth of SCC in mice, indicating that immunogenic apoptotic cells can activate an effective antitumor adaptive immunity and lead to a DC vaccine-based cancer immunotherapy.
June 2016: Oncoimmunology
Sadahiro Kaneko, Sadao Kaneko
Malignant gliomas are extremely difficult to treat with no specific curative treatment. On the other hand, photodynamic medicine represents a promising technique for neurosurgeons in the treatment of malignant glioma. The resection rate of malignant glioma has increased from 40% to 80% owing to 5-aminolevulinic acid-photodynamic diagnosis (ALA-PDD). Furthermore, ALA is very useful because it has no serious complications. Based on previous research, it is apparent that protoporphyrin IX (PpIX) accumulates abundantly in malignant glioma tissues after ALA administration...
2016: International Journal of Biomedical Imaging
Dafeng Chu, Qi Zhao, Jian Yu, Faya Zhang, Hui Zhang, Zhenjia Wang
Cancer immunotherapy using tumor-specific monoclonal antibodies presents a novel approach for cancer treatment. A monoclonal antibody TA99 specific for gp75 antigen of melanoma initiates neutrophil recruitment in tumor responsible for cancer therapy. Here, a strategy is reported for hijacking neutrophils in vivo using nanoparticles (NPs) to deliver therapeutics into tumor. In a mouse model of melanoma, it is shown that systemically delivered albumin NPs increase in tumor when TA99 antibody is injected; and the NP tumor accumulation is mediated by neutrophils...
May 2016: Advanced Healthcare Materials
Abhishek D Garg, Lien Vandenberk, Carolien Koks, Tina Verschuere, Louis Boon, Stefaan W Van Gool, Patrizia Agostinis
The promise of dendritic cell (DC)-based immunotherapy has been established by two decades of translational research. Of the four malignancies most targeted with clinical DC immunotherapy, high-grade glioma (HGG) has shown the highest susceptibility. HGG-induced immunosuppression is a roadblock to immunotherapy, but may be overcome by the application of T helper 1 (T(H)1) immunity-biased, next-generation, DC immunotherapy. To this end, we combined DC immunotherapy with immunogenic cell death (ICD; a modality shown to induce T(H)1 immunity) induced by hypericin-based photodynamic therapy...
March 2, 2016: Science Translational Medicine
Verena von Felbert, Dirk Bauerschlag, Nicolai Maass, Karen Bräutigam, Ivo Meinhold-Heerlein, Mira Woitok, Stefan Barth, Ahmad Fawzi Hussain
PURPOSE: The term "theranostics" represents a new paradigm in medicine especially for cancer treatment. This term was coined by Funkhouser in 2002 and defines a reagent that combines therapeutic and diagnostic properties. It is widely believed that theranostics agents will have considerable impact on healthcare before, during, and after disease by improving cancer prognosis and management simultaneously. Current theranostics approaches still rely on passive tumor targeting strategies, which have scattergun effects and tend to damage both neoplastic and non-neoplastic cells...
May 2016: Journal of Cancer Research and Clinical Oncology
Yuanhong Zheng, Guifang Yin, Vanminh Le, Anle Zhang, Siyu Chen, Xin Liang, Jianwen Liu
Photodynamic therapy (PDT), a regulatory approved cancer treatment, is reported to be capable of causing immunogenic apoptosis. The current data reveal PDT can cause the dysregulation of "eat me" and "don't eat me" signal by generating reactive oxygen species (ROS) -mediated endoplasmic reticulum (ER) stress. This dysregulation probably contribute to the increased uptake of PDT-killed Lewis lung carcinoma (LLC) cells by homologous dendritic cells (DCs), accompanied by phenotypic maturation (CD80(high), CD86(high), and CD40(high)) and functional stimulation (NO(high), IL-10(absent)) of dendritic cells as well as subsequent T-cell responses...
2016: International Journal of Biological Sciences
Jan-Friedrich Jokisch, Alexander Karl, Christian Stief
INTRODUCTION: Nonmuscle invasive urothelial cell carcinoma is the most frequent malignancy of the urinary bladder. The high recurrence rate (up to 80%) and risk of progression (up to 30%) reflect the need for long-term follow-up and sometimes multiple interventions. To reduce the rate of recurrences and tumor progression, intravesical immunotherapy, especially the use of Bacille Calmette-Guerin (BCG), represents the gold standard adjuvant treatment of high-risk nonmuscle invasive bladder cancer (NMIBC)...
October 2015: Indian Journal of Urology: IJU: Journal of the Urological Society of India
Joanna Marczynska, Magdalena Banas, Krzysztof Guzik, Michal Koltun, Pawel Majewski, Joanna Cichy, Martyna Krzykawska-Serda, Anna Makarska, Mateusz Kwitniewski
After years of setbacks, therapeutic cancer vaccines have become an alternative treatment option. Among the diversity of targeted tumour associated antigens (TAA), cancer-testis antigens (CTAs) are promising targets for cancer immunotherapy because they are highly immunogenic; meanwhile, they are expressed in human tumours of different histological origin but not in adult somatic tissues. Epigenetic modifications, such as DNA methylation, regulate CTAs expression both in normal and cancer cells. 5-Aza-2'-deoxycytidine (5-AZA-CdR), a DNA hypomethylating drug, induces the expression of CTAs in neoplastic cells...
December 2015: Journal of Photochemistry and Photobiology. B, Biology
Mladen Korbelik, Judit Banáth, Kyi Min Saw
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...
2015: International Journal of Molecular Sciences
Jan Willem Kleinovink, Pieter B van Driel, Thomas J Snoeks, Natasa Prokopi, Marieke F Fransen, Luis J Cruz, Laura Mezzanotte, Alan Chan, Clemens W Löwik, Ferry Ossendorp
PURPOSE: The efficacy of immunotherapy against advanced cancer may be improved by combination strategies. Photodynamic therapy (PDT) is a local tumor ablation method based on localized activation of a photosensitizer, leading to oxygen radical-induced tumor cell death. PDT can enhance antitumor immune responses by release of antigen and danger signals, supporting combination protocols of PDT with immunotherapy. EXPERIMENTAL DESIGN: We investigated the local and systemic immune effects of PDT after treatment of established tumors...
March 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
O Tyurikova, Y Dembitskaya, K Yashin, M Mishchenko, M Vedunova, I Medyanik, V Kazantsev
Amongst large a variety of oncological diseases, malignant gliomas represent one of the most severe types of tumors. They are also the most common type of the brain tumors and account for over half of the astrocytic tumors. According to different sources, the average life expectancy of patients with various glioblastomas varies between 10 and 12 months and that of patients with anaplastic astrocytic tumors between 20 and 24 months. Therefore, studies of the physiology of transformed glial cells are critical for the development of treatment methods...
2015: Computational and Mathematical Methods in Medicine
Abhishek D Garg, Sanne Elsen, Dmitri V Krysko, Peter Vandenabeele, Peter de Witte, Patrizia Agostinis
Immunogenic cell death (ICD) is a well-established instigator of 'anti-cancer vaccination-effect (AVE)'. ICD has shown considerable preclinical promise, yet there remain subset of cancer patients that fail to respond to clinically-applied ICD inducers. Non-responsiveness to ICD inducers could be explained by the existence of cancer cell-autonomous, anti-AVE resistance mechanisms. However such resistance mechanisms remain poorly investigated. In this study, we have characterized for the first time, a naturally-occurring preclinical cancer model (AY27) that exhibits intrinsic anti-AVE resistance despite treatment with ICD inducers like mitoxantrone or hypericin-photodynamic therapy...
September 29, 2015: Oncotarget
Malgorzata Wachowska, Angelika Muchowicz, Jakub Golab
Photodynamic therapy (PDT) of cancer is an approved therapeutic procedure that generates oxidative stress leading to cell death of tumor and stromal cells. Cell death resulting from oxidative damage to intracellular components leads to the release of damage-associated molecular patterns (DAMPs) that trigger robust inflammatory response and creates local conditions for effective sampling of tumor-associated antigens (TAA) by antigen-presenting cells. The latter can trigger development of TAA-specific adaptive immune response...
2015: Frontiers in Oncology
Janusz M Dąbrowski, Luis G Arnaut
Photodynamic therapy (PDT) requires a medical device, a photosensitizing drug and adequate use of both to trigger biological mechanisms that can rapidly destroy the primary tumour and provide long-lasting protection against metastasis. We present a multidisciplinary view of the issues raised by the development of PDT. We show how spectroscopy, photophysics, photochemistry and pharmacokinetics of photosensitizers determine the mechanism of cell death and clinical protocols. Various examples of combinations with chemotherapies and immunotherapies illustrate the opportunities to potentiate the outcome of PDT...
October 2015: Photochemical & Photobiological Sciences
Jesse M Lewin, John A Carucci
Basal cell carcinoma (BCC), a malignant neoplasm derived from non-keratinizing cells that originate in the basal layer of the epidermis, is the most common cancer in humans. Several factors such as anatomic location, histologic features, primary or recurrent tumors, and patient characteristics influence the choice of treatment modality for BCC. Mohs micrographic surgery (MMS) facilitates optimal margin control and conservation of normal tissue for the management of BCC; however, other treatment modalities may also be implemented in the correct clinical scenario...
2015: F1000Prime Reports
Guizhi Zhu, Gang Niu, Xiaoyuan Chen
Western medicine often aims to specifically treat diseased tissues or organs. However, the majority of current therapeutics failed to do so owing to their limited selectivity and the consequent "off-target" side effects. Targeted therapy aims to enhance the selectivity of therapeutic effects and reduce adverse side effects. One approach toward this goal is to utilize disease-specific ligands to guide the delivery of less-specific therapeutics, such that the therapeutic effects can be guided specifically to diseased tissues or organs...
November 18, 2015: Bioconjugate Chemistry
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