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Immunogenic cell death

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https://www.readbyqxmd.com/read/28218037/immunotoxin-a-new-tool-for-cancer-therapy
#1
Hossein Allahyari, Sahar Heidari, Mehdi Ghamgosha, Parvaneh Saffarian, Jafar Amani
Cancer is one of the main reasons of death in the most countries and in Iran. Immunotherapy quickly became one of the best methods of cancer treatment, along with chemotherapy and radiation. "Immunotoxin Therapy" is a promising way of cancer therapy that is mentioned in this field. Immunotoxins are made from a toxin attaching to an antibody target proteins present on cancer cells. The first-generation immunotoxins were made of a full-length toxin attached to whole monoclonal antibodies. But, these immunotoxins could bind to normal cells...
February 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28216187/recombinant-proteins-of-zaire-ebolavirus-induce-potent-humoral-and-cellular-immune-responses-and-protect-against-live-virus-infection-in-mice
#2
Axel T Lehrer, Teri-Ann S Wong, Michael M Lieberman, Tom Humphreys, David E Clements, Russell R Bakken, Mary Kate Hart, William D Pratt, John M Dye
Infections with filoviruses in humans are highly virulent, causing hemorrhagic fevers which result in up to 90% mortality. In addition to natural infections, the ability to use these viruses as bioterrorist weapons is of significant concern. Currently, there are no licensed vaccines or therapeutics available to combat these infections. The pathogenesis of disease involves the dysregulation of the host's immune system, which results in impairment of the innate and adaptive immune responses, with subsequent development of lymphopenia, thrombocytopenia, hemorrhage, and death...
February 16, 2017: Vaccine
https://www.readbyqxmd.com/read/28215530/rationale-for-the-combination-of-dendritic-cell-based-vaccination-approaches-with-chemotherapy-agents
#3
I Truxova, M Hensler, P Skapa, M J Halaska, J Laco, A Ryska, R Spisek, J Fucikova
Owing to their central role in the initiation and regulation of antitumor immunity, dendritic cells (DCs) have been widely tested for use in cancer immunotherapy. Despite several encouraging clinical applications, existing DC-based immunotherapy efforts have yielded inconsistent results. Recent work has identified strategies that may allow for more potent DC-based vaccines, such as the combination with antitumor agents that have the potential to synergistically enhance DC functions. Selected cytotoxic agents may stimulate DCs either by directly promoting their maturation or through the induction of immunogenic tumor cell death...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28197379/caspase-2-and-oxidative-stress-underlie-the-immunogenic-potential-of-high-hydrostatic-pressure-induced-cancer-cell-death
#4
Irena Moserova, Iva Truxova, Abhishek D Garg, Jakub Tomala, Patrizia Agostinis, Pierre Francois Cartron, Sarka Vosahlikova, Marek Kovar, Radek Spisek, Jitka Fucikova
High hydrostatic pressure (HHP) promotes key characteristics of immunogenic cell death (ICD), in thus far resembling immunogenic chemotherapy and ionizing irradiation. Here, we demonstrate that cancer cells succumbing to HHP induce CD4(+) and CD8(+) T cell-dependent protective immunity in vivo. Moreover, we show that cell death induction by HHP relies on the overproduction of reactive oxygen species (ROS), causing rapid establishment of the integrated stress response, eIF2α phosphorylation by PERK, and sequential caspase-2, -8 and -3 activation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28187172/generation-of-dendritic-cell-based-vaccine-using-high-hydrostatic-pressure-for-non-small-cell-lung-cancer-immunotherapy
#5
Nada Hradilova, Lenka Sadilkova, Ondrej Palata, Dagmar Mysikova, Hana Mrazkova, Robert Lischke, Radek Spisek, Irena Adkins
High hydrostatic pressure (HHP) induces immunogenic death of tumor cells which confer protective anti-tumor immunity in vivo. Moreover, DC pulsed with HHP-treated tumor cells induced therapeutic effect in mouse cancer model. In this study, we tested the immunogenicity, stability and T cell stimulatory activity of human monocyte-derived dendritic cell (DC)-based HHP lung cancer vaccine generated in GMP compliant serum free medium using HHP 250 MPa. DC pulsed with HHP-killed lung cancer cells and poly(I:C) enhanced DC maturation, chemotactic migration and production of pro-inflammatory cytokines after 24h...
2017: PloS One
https://www.readbyqxmd.com/read/28152048/zika-virus-antagonizes-type-i-interferon-responses-during-infection-of-human-dendritic-cells
#6
James R Bowen, Kendra M Quicke, Mohan S Maddur, Justin T O'Neal, Circe E McDonald, Nadia B Fedorova, Vinita Puri, Reed S Shabman, Bali Pulendran, Mehul S Suthar
Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that is causally linked to severe neonatal birth defects, including microcephaly, and is associated with Guillain-Barre syndrome in adults. Dendritic cells (DCs) are an important cell type during infection by multiple mosquito-borne flaviviruses, including dengue virus, West Nile virus, Japanese encephalitis virus, and yellow fever virus. Despite this, the interplay between ZIKV and DCs remains poorly defined. Here, we found human DCs supported productive infection by a contemporary Puerto Rican isolate with considerable variability in viral replication, but not viral binding, between DCs from different donors...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28151483/colon-cancer-cell-treatment-with-rose-bengal-generates-a-protective-immune-response-via-immunogenic-cell-death
#7
Jianzhong Qin, Nicholas Kunda, Guilin Qiao, Jed F Calata, Krunal Pardiwala, Bellur S Prabhakar, Ajay V Maker
Immunotherapeutic approaches to manage patients with advanced gastrointestinal malignancies are desired; however, mechanisms to incite tumor-specific immune responses remain to be elucidated. Rose bengal (RB) is toxic at low concentrations to malignant cells and may induce damage-associated molecular patterns; therefore, we investigated its potential as an immunomodulator in colon cancer. Murine and human colon cancer lines were treated with RB (10% in saline/PV-10) for cell cycle, cell death, and apoptosis assays...
February 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28151378/checkpoint-inhibition-new-treatment-options-in-urologic-cancer
#8
Daan Joost De Maeseneer, Brant Delafontaine, Sylvie Rottey
Both urothelial (UC) and renal cell cancer (RCC) are highly immunogenic tumours. Recent advances in cellular immunity understanding have resulted in a successful new class of therapeutic agents. Interaction between the programmed cell death 1 (PD1) on regulatory T-cells (Treg) and programmed cell death 1 ligand (PDL1) on cancer cells inhibits an effective immune response and is an important mechanism for cancer cells to evade the immune system. Monoclonal anti-PD1 and anti-PDL1 antibodies inhibit this interaction and are called checkpoint inhibitors...
February 2017: Acta Clinica Belgica
https://www.readbyqxmd.com/read/28137295/a-phase-ii-trial-of-stereotactic-body-radiotherapy-with-concurrent-anti-pd1-treatment-in-metastatic-melanoma-evaluation-of-clinical-and-immunologic-response
#9
Katrien De Wolf, Vibeke Kruse, Nora Sundahl, Mireille van Gele, Ines Chevolet, Reinhart Speeckaert, Lieve Brochez, Piet Ost
BACKGROUND: Antibodies blocking programmed cell death 1 (PD-1) have encouraging responses in patients with metastatic melanoma. Response to anti-PD-1 treatment requires pre-existing CD8+ T cells that are negatively regulated by PD-1-mediated adaptive immune resistance. Unfortunately, less than half of melanoma tumours have these characteristics. Combining anti-PD-1 treatment with other immunomodulating treatments to activate CD8+ T cells is therefore of vital importance to increase response rates and long-term survival benefit in melanoma patients...
January 31, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28128712/next-generation-dendritic-cell-based-vaccines-for-leukemia-patients
#10
Jean-Marc Hoffmann, Michael Schmitt, Ming Ni, Anita Schmitt
Up to today treatment of leukemia patients remains challenging and different therapies have been developed, among them the generation of dendritic cell (DC) vaccines. DCs, highly specific for immunogenic cancer antigens, are generated either ex vivo or in vivo and boost the immune response against leukemic cells. Nevertheless, response rates are still heterogeneous and DC vaccines need improvement. New methods for generating DC vaccines have been summed up under the term 'next-generation DC vaccines'. They range from the analysis of human leukocyte antigen-ligandomes to immunogenic cell death inducers, from the production of viral vectors to mRNA transfection and finally from delivering peptides to DCs in vivo through either antibodies or cell-penetrating peptides...
January 2017: Immunotherapy
https://www.readbyqxmd.com/read/28126499/bacillus-calmette-guerin-improves-local-and-systemic-response-to-radiotherapy-in-invasive-bladder-cancer
#11
Barbara Prack Mc Cormick, Denise Belgorosky, Yanina Langle, Natalia Balarino, Eduardo Sandes, Ana María Eiján
BACKGROUND: A key factor contributing to radio-resistance in conservative invasive bladder cancer (BCa) treatment is tumor hypoxia and a strategy to overcome it is to trigger the production of nitric oxide (NO). On the other hand, ionizing radiation (IR) applied to a primary tumor can induce immunogenic cell death which may set off a cytotoxic immune response against the primary tumor and its metastasis. PURPOSE: To study in vitro and in vivo, the role of BCG as a local sensitizer to overcome hypoxia-associated radio-resistance through the production of NO, and as an immune-stimulator to be used in combination with IR to generate a local tumor vaccine for invasive BCa treatment...
January 23, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28122343/targeted-breast-cancer-therapy-by-harnessing-the-inherent-blood-group-antigen-immune-system
#12
Wei Han, Wei Li, Xiaoying Zhang, Zhonghua Du, Xiaoliang Liu, Xin Zhao, Xue Wen, Guanjun Wang, Ji-Fan Hu, Jiuwei Cui
Cancer gene therapy has attracted increasing attention for its advantages over conventional therapy in specific killing of tumor cells. Here, we attempt to prove a novel therapeutic approach that targets tumors by harnessing the blood antigen immune response system, which is inherently present in patients with breast cancers. Breast cancer MDA-MB-231 cells expressed blood group H antigen precursor. After ectopic expression of blood group A glycosyltransferase, we found that the H precursor was converted into the group A antigen, appearing on the surface of tumor cells...
January 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28118938/an-accelerated-rabies-vaccine-schedule-based-on-toll-like-receptor-3-tlr3-agonist-pika-adjuvant-augments-rabies-virus-specific-antibody-and-t-cell-response-in-healthy-adult-volunteers
#13
Limin Wijaya, Christine Y L Tham, Yvonne F Z Chan, Abigail W L Wong, L T Li, Lin-Fa Wang, Antonio Bertoletti, Jenny G Low
BACKGROUND: Rabies is a fatal disease where post-exposure prophylaxis (PEP) is crucial in preventing infection. However, deaths even after appropriate PEP, have been reported. The PIKA Rabies vaccine adjuvant is a TLR3 agonist that activates B and T cells leading to a robust immune response. METHODS: We conducted a phase I, open label, randomized study in healthy adults to assess the safety and immunogenicity of the PIKA Rabies vaccine and an accelerated vaccine regimen...
February 22, 2017: Vaccine
https://www.readbyqxmd.com/read/28088478/comparison-of-the-adjuvant-activity-of-emulsions-with-different-physicochemical-properties-on-the-antibody-response-towards-the-venom-of-west-african-carpet-viper-echis-ocellatus
#14
Juan Manuel Valverde, Karina Rodríguez, María Herrera, Álvaro Segura, Mariángela Vargas, Mauren Villalta, Mavis Montero, Jose María Gutiérrez, Guillermo León
Adjuvant emulsions are widely used to enhance the antibody response of the animals used as immunoglobulin source for producing antivenoms. Usually, the adjuvant activity of emulsions is attributed both to their ability to trigger "danger" signals from cells in which they induce death, and to form depots from which immunogens are slowly released. However, there is contradictory evidence suggesting that adjuvant activity of emulsions is independent of the dispersion type and the rate of immunogen release. In order to test how physical properties of emulsions, composed of mineral oil and water, affect their ability to enhance the antibody response towards snake venoms, we compared water-in-oil (W/O) emulsions prepared at volume ratios of 70/30, 50/50 or 30/70, a 50/50 oil-in-water (O/W) emulsion, and a water-in-oil-in-water (W/O/W) multiple emulsion...
January 12, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28079009/emerging-roles-of-calreticulin-in-cancer-implications-for-therapy
#15
Kavya Venkateswaran, Amit Verma, Anant Narayan Bhatt, Anju Shrivastava, Kailash Manda, Hanumantharao G Raj, Ashok Prasad, Christophe Len, Virinder S Parmar, Bilikere Dwarakanath
Calreticulin (CRT), initially identified as a ubiquitous calcium-binding protein in the endoplasmic reticulum, has emerged as a multifunctional protein with roles in calcium homeostasis, molecular chaperoning and cell adhesion. Emerging evidence suggests its involvement in tumorigenesis facilitating proliferation, migration, and adhesion. CRT translocated to the cell surface (ecto-CRT) serves as a phagocytic signal for immunogenic cell death (ICD) mediated through dendritic cells (DCs) and cytotoxic T-cell activation thereby making tumors susceptible to immunotherapy-based anti-cancer strategies...
11, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28075526/cetuximab-strongly-enhances-immune-cell-infiltration-into-liver-metastatic-sites-in-colorectal-cancer
#16
Yuka Inoue, Shoichi Hazama, Nobuaki Suzuki, Yukio Tokumitsu, Shinsuke Kanekiyo, Shinobu Tomochika, Ryouichi Tsunedomi, Yoshihiro Tokuhisa, Michihisa Iida, Kazuhiko Sakamoto, Shigeru Takeda, Tomio Ueno, Shigefumi Yoshino, Hiroaki Nagano
Cetuximab has activity against colorectal cancers. Recent studies demonstrated that cetuximab induces antibody-dependent cell-mediated cytotoxicity via immune cells, and a new immune-related mechanism of inducing immunogenic cell death. This study aimed to evaluate the immune responses induced by cetuximab in tumor microenvironments at liver metastasis sites of metastatic colorectal cancer patients. We assessed immune cell infiltration in the liver metastatic sites of 53 colorectal cancer patients. These patients were divided into three groups according to the treatment before operation: chemotherapy with cetuximab, chemotherapy without cetuximab, and no chemotherapy...
January 11, 2017: Cancer Science
https://www.readbyqxmd.com/read/28073774/temporally-distinct-pd-l1-expression-by-tumor-and-host-cells-contributes-to-immune-escape
#17
Takuro Noguchi, Jeffrey P Ward, Matthew M Gubin, Cora D Arthur, Sang Hun Lee, Jasreet Hundal, Mark J Selby, Robert F Graziano, Elaine R Mardis, Alan J Korman, Robert D Schreiber
Antibody blockade of programmed death-1 (PD-1) or its ligand, PD-L1, has led to unprecedented therapeutic responses in certain tumor-bearing individuals, but PD-L1 expression's prognostic value in stratifying cancer patients for such treatment remains unclear. Reports conflict on the significance of correlations between PD-L1 on tumor cells and positive clinical outcomes to PD-1/PD-L1 blockade. We investigated this issue using genomically related, clonal subsets from the same methylcholanthrene-induced sarcoma: a highly immunogenic subset that is spontaneously eliminated in vivo by adaptive immunity and a less immunogenic subset that forms tumors in immunocompetent mice, but is sensitive to PD-1/PD-L1 blockade therapy...
February 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28069136/the-inflammatory-signal-adaptor-ripk3-functions-beyond-necroptosis
#18
K Moriwaki, F K-M Chan
Receptor interacting protein kinase 3 (RIPK3) is an essential serine/threonine kinase for necroptosis, a type of regulated necrosis. A variety of stimuli can cause RIPK3 activation through phosphorylation. Activated RIPK3 in turn phosphorylates and activates the downstream necroptosis executioner mixed lineage kinase domain-like (MLKL). Necroptosis is a highly inflammatory type of cell death because of the release of intracellular immunogenic contents from disrupted plasma membrane. Indeed, RIPK3-deficient mice exhibited reduced inflammation in many inflammatory disease models...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28060726/immunogenic-cancer-cell-death-selectively-induced-by-near-infrared-photoimmunotherapy-initiates-host-tumor-immunity
#19
Mikako Ogawa, Yusuke Tomita, Yuko Nakamura, Min-Jung Lee, Sunmin Lee, Saori Tomita, Tadanobu Nagaya, Kazuhide Sato, Toyohiko Yamauchi, Hidenao Iwai, Abhishek Kumar, Timothy Haystead, Hari Shroff, Peter L Choyke, Jane B Trepel, Hisataka Kobayashi
Immunogenic cell death (ICD) is a form of cell death that activates an adaptive immune response against dead-cell-associated antigens. Cancer cells killed via ICD can elicit antitumor immunity. ICD is efficiently induced by near-infrared photo-immunotherapy (NIR-PIT) that selectively kills target-cells on which antibody-photoabsorber conjugates bind and are activated by NIR light exposure. Advanced live cell microscopies showed that NIR-PIT caused rapid and irreversible damage to the cell membrane function leading to swelling and bursting, releasing intracellular components due to the influx of water into the cell...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28052254/pan-cancer-immunogenomic-analyses-reveal-genotype-immunophenotype-relationships-and-predictors-of-response-to-checkpoint-blockade
#20
Pornpimol Charoentong, Francesca Finotello, Mihaela Angelova, Clemens Mayer, Mirjana Efremova, Dietmar Rieder, Hubert Hackl, Zlatko Trajanoski
The Cancer Genome Atlas revealed the genomic landscapes of human cancers. In parallel, immunotherapy is transforming the treatment of advanced cancers. Unfortunately, the majority of patients do not respond to immunotherapy, making the identification of predictive markers and the mechanisms of resistance an area of intense research. To increase our understanding of tumor-immune cell interactions, we characterized the intratumoral immune landscapes and the cancer antigenomes from 20 solid cancers and created The Cancer Immunome Atlas (https://tcia...
January 3, 2017: Cell Reports
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