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Specific immunotherapy

Lan Huang, Huaxi Xu, Guangyong Peng
Cellular energy metabolism not only promotes tumor cell growth and metastasis but also directs immune cell survival, proliferation and the ability to perform specific and functional immune responses within the tumor microenvironment. A better understanding of the molecular regulation of metabolism in different cell components in the tumor-suppressive microenvironment is critical for the development of effective strategies for human cancer treatments. Toll-like receptors (TLRs) have recently been recognized as critical factors involved in tumor pathogenesis, regulating both tumor cells and tumor-infiltrating innate and adaptive immune cells...
March 19, 2018: Cellular & Molecular Immunology
E Savi, S Peveri, C Cavaliere, S Masieri, M Montagni
The introduction of highly purified natural and recombinant single allergenic molecules represented an important improvement in the diagnosis of IgE sensitization. The identification of specific IgE against cross-reacting molecules such as profilin, lipid transfer proteins, calcium binding proteins or against “genuine molecules”, represents an added value and allows to distinguish between true and false polysensitization. In vitro tests add information to recognize patients with sensitization to genuine molecules that cause allergic diseases and to evaluate in childhood the spreading of sensitization for each molecule in order to choose the best treatment and to identify the ideal patient for allergen immunotherapy...
January 2018: Journal of Biological Regulators and Homeostatic Agents
Zhongzhen Yi, Brooke L Prinzing, Felicia Cao, Stephen Gottschalk, Giedre Krenciute
Glioblastoma is the most aggressive primary brain tumor in humans and is virtually incurable with conventional therapies. Chimeric antigen receptor (CAR) T cell therapy targeting the glioblastoma antigen EphA2 is an attractive approach to improve outcomes because EphA2 is expressed highly in glioblastoma but only at low levels in normal brain tissue. Building upon our previous findings in this area, we generated and evaluated a panel of EphA2-specific CARs. We demonstrate here that T cells expressing CD28...
June 15, 2018: Molecular Therapy. Methods & Clinical Development
Jan Aleksander Kraśko, Karolina Žilionytė, Adas Darinskas, Neringa Dobrovolskienė, Agata Mlynska, Svetlana Riabceva, Iosif Zalutsky, Marina Derevyanko, Vladimir Kulchitsky, Olga Karaman, Natalia Fedosova, Tatiana Vasyliyvna Symchych, Gennady Didenko, Vasyl Chekhun, Marius Strioga, Vita Pašukonienė
Immunotherapy in the form of anticancer vaccination relies on the mobilization of the patient's immune system against specific cancer antigens. Instead of focusing on an autologous cell lysate, which is not always available in clinical practice, the present study investigates vaccines utilizing xenogeneic foetal tissue that are rich in oncofoetal antigens. Lewis lung carcinoma (LLC)-challenged C57BL/6 mice were treated with either a xenogeneic vaccine made from chicken whole embryo, or a xenogeneic vaccine made from rat embryonic brain tissue, supplemented with a Bacillus subtilis protein fraction as an adjuvant...
April 2018: Oncology Letters
Fen Huang, Bo Wang, Jiangzheng Zeng, Shenggang Sang, Junhua Lei, Yanda Lu
Programmed cell death-1 (PD-1) is an oncogene associated with suppressing proliferation and cytokine production of T cells in the progression of liver cancer. microRNAs (miRs) regulate gene expression via specific binding to the target 3'untranslated region of mRNA. In the present study, miR-374b was indicated to interact with PD-1 and affect the tumor-targeting capacity of cytokine-induced killer (CIK) cells. miR-374b inhibitor significantly increased PD-1 expression in CIK cells. A synthetic small interfering (si)RNA targeting PD-1 was employed to silence the expression level of PD-1 in CIK cells...
April 2018: Oncology Letters
Jessica Da Gama Duarte, Sagun Parakh, Miles C Andrews, Katherine Woods, Anupama Pasam, Candani Tutuka, Simone Ostrouska, Jonathan M Blackburn, Andreas Behren, Jonathan Cebon
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced melanoma. The first ICI to demonstrate clinical benefit, ipilimumab, targets cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4); however, the long-term overall survival is just 22%. More than 40 years ago intralesional (IL) bacillus Calmette-Guérin (BCG), a living attenuated strain of Mycobacterium bovis , was found to induce tumor regression by stimulating cell-mediated immunity following a localized and self-limiting infection...
2018: Frontiers in Immunology
Hamid Emamekhoo, Puneet Dhillon, Dharmesh Gopalakrishnan, Paul Elson, Andrew Stephenson, Cristina Magi-Galluzzi, Jesse McKenney, Holly Harper, Georges-Pascal Haber, Jihad Kaouk, Byron Lee, Amr Fergany, Ryan Berglund, Michael Gong, Robert Stein, Venkatesh Krishnamurthi, Timothy Gilligan, Moshe Ornstein, Brian Rini, Jorge Garcia, Petros Grivas
BACKGROUND: Upper tract urothelial carcinoma (UTUC) accounts for approximately 5% of all urothelial cancers. Because of similarities in morphology and histology between UTUC and urothelial carcinoma of the bladder, most treatment guidelines used for UTUC are extrapolated from the urothelial bladder carcinoma setting. With the emergence of new treatment modalities, such as immunotherapy, UTUC-specific prognostic and predictive models are needed. PATIENTS AND METHODS: A retrospective study of 454 UTUC patients who received surgery at Cleveland Clinic (1995-2014) was conducted...
February 6, 2018: Clinical Genitourinary Cancer
Mika J Mäkelä, Pär Gyllfors, Erkka Valovirta, Maria A Steffensen, Pernille M Grønager, Johannes Savolainen, Lone Winther
PURPOSE: The SQ tree sublingual immunotherapy (SLIT)-tablet containing allergen extracts with the major allergen Bet v 1 from birch pollen is currently being developed for the treatment of tree pollen-induced allergic rhinitis/conjunctivitis with or without asthma. The aim of this Phase II trial was to investigate the dose-related efficacy and safety of the SQ tree SLIT-tablet. METHODS: This study was a randomized, parallel-group, double-blind, placebo-controlled, multi-national trial conducted in Europe...
March 15, 2018: Clinical Therapeutics
Xueting Liu, Liping Zeng, Zhongqiu Zhao, Yang Xie, Shan Wang, Junyan Zhang, Ying He, Zehong Zou, Jianguo Zhang, Ailin Tao
Staphylococcal enterotoxin A is well known as a superantigen and able to be used for cancer immunotherapy. In this study, recombinant Staphylococcal enterotoxin A was genetically conjugated to epidermal growth factor to produce a chimeric protein recombinant Staphylococcal enterotoxin A-epidermal growth factor expressed in Escherichia coli. The recombinant Staphylococcal enterotoxin A-epidermal growth factor protein was purified using Strep-Tactin affinity chromatography and Endotoxin Removal Resin and identified by sodium dodecyl sulfate-polyacrylamide gel electropheresis and liquid chromatography-tandem mass spectrometry analysis...
January 1, 2018: Technology in Cancer Research & Treatment
Tae Beom Kim, Young Sup Shim, Sang Min Lee, Eun Suk Son, Jung Woo Shim, Sang Pyo Lee
Post-orgasmic illness syndrome (POIS) is a very rare disease characterized by local allergic symptoms and transient flu-like illness that nearly always occur after masturbation, coitus, or spontaneous ejaculation and last for 2 to 7 days. In a previous case report, 2 patients with POIS received hyposensitization therapy composed of multiple subcutaneous injections of autologous semen that resulted in a gradual decrease of symptoms. However, this procedure requires patients to endure pain and discomfort during frequent subcutaneous injections and preceding masturbations to obtain the autologous semen used for therapy...
March 14, 2018: Sexual Medicine
Aurélien Gobert, Marianne Veyri, Isabelle Poizot-Martin, Armelle Lavolé, Caroline Solas, Romain Paliche, Christine Katlama, Dominique Costagliola, Jean-Philippe Spano
Since the era of combined antiretroviral therapy, life expectancy of people living with HIV has been improved and is associated with a change in causes of death. Cancer, both AIDS-defining or non-AIDS-defining cancers, has become the leading cause of death in people living with HIV associated with an increase in the incidence of some cancers compared to the general population. Epidemiology and the identification of risk factors is a crucial issue, particularly to determine the most appropriate prevention and screening strategies in this population...
March 13, 2018: Bulletin du Cancer
Hannah R Wardill, Ysabella Z A Van Sebille, Matthew A Ciorba, Joanne M Bowen
PURPOSE OF REVIEW: Strong preclinical data support prophylactic probiotics as an effective preventive strategy for diarrhoea secondary to anticancer therapies. To determine the composite evidence that this approach translates to the clinic, we performed a meta-analysis of randomized controlled trials (RCTs) of prophylactic probiotics for the prevention of cancer therapy induced diarrhoea. RECENT FINDINGS: A three-step search strategy was used to identify relevant studies (1 June 2000-1 June 2017) investigating probiotic intervention for diarrhoea secondary to any cancer therapy (cytotoxic, targeted and immunotherapies)...
March 14, 2018: Current Opinion in Supportive and Palliative Care
Ari Rosenberg, Mark Agulnik
Epithelioid hemangioendothelioma (EHE) is an extremely rare sarcoma, as such it can pose a clinical dilemma based solely on its rarity. Also, the spectrum of disease varies greatly between an indolent disease and aggressive disease with widespread metastases. In our clinical practice, the primary focus has been to get a handle on the aggressive nature of the disease, which will then dictate how urgently one needs to treat the patient. Pathological review with immunohistochemistry and molecular characterization is paramount...
March 15, 2018: Current Treatment Options in Oncology
Vivek Murthy, Janna Minehart, Daniel H Sterman
Modern cancer immunotherapies represent a major shift in paradigm with respect to how we understand innate and adaptive responses to malignancy. Successful tumors co-opt normal immunosurveillance mechanisms by potent interactions between the tumor and local draining lymph nodes. Tumor cells mediate a complex and dynamic immunoediting procedure that results in increased vascular efflux into the draining lymphatics, an immunosuppressive microenvironment rich in regulatory T-lymphocytes, dysfunctional antigen presentation, and downregulation of normal effector lymphocyte responses...
December 1, 2017: Journal of the National Cancer Institute
Mark Owyong, Gizem Efe, Michael Owyong, Aamna J Abbasi, Vaishnavi Sitarama, Vicki Plaks
There is a growing list of cancer immunotherapeutics approved for use in a population with an increasing number of aged individuals. Cancer immunotherapy (CIT) mediates tumor destruction by activating anti-tumor immune responses that have been silenced through the oncogenic process. However, in an aging individual, immune deregulation is positively correlated with age. In this context, it is vital to examine the age-related changes in the tumor microenvironment (TME) and specifically, those directly affecting critical players to ensure CIT efficacy...
2018: Frontiers in Cell and Developmental Biology
Sara Bobisse, Raphael Genolet, Annalisa Roberti, Janos L Tanyi, Julien Racle, Brian J Stevenson, Christian Iseli, Alexandra Michel, Marie-Aude Le Bitoux, Philippe Guillaume, Julien Schmidt, Valentina Bianchi, Denarda Dangaj, Craig Fenwick, Laurent Derré, Ioannis Xenarios, Olivier Michielin, Pedro Romero, Dimitri S Monos, Vincent Zoete, David Gfeller, Lana E Kandalaft, George Coukos, Alexandre Harari
Immunotherapy directed against private tumor neo-antigens derived from non-synonymous somatic mutations is a promising strategy of personalized cancer immunotherapy. However, feasibility in low mutational load tumor types remains unknown. Comprehensive and deep analysis of circulating and tumor-infiltrating lymphocytes (TILs) for neo-epitope specific CD8+ T cells has allowed prompt identification of oligoclonal and polyfunctional such cells from most immunotherapy-naive patients with advanced epithelial ovarian cancer studied...
March 15, 2018: Nature Communications
Rosy Wells, A T Fox, Mark Furman
Case reports have described an association between oral food/aeroallergen immunotherapy with the development of eosinophilic oesophagitis (EoE). The underlying mechanism of this is poorly understood, as is the role that both food/aeroallergen sensitisation plays in the pathogenesis of EoE. Specific immunotherapy has a long-standing history of use in the management of moderate/severe seasonal allergic rhinitis (AR), caused by tree/grass pollens. Subcutaneous immunotherapy (SCIT) to grass pollen is less commonly used in children than sublingual immunotherapy (SLIT) or oral immunotherapy for practical reasons...
March 15, 2018: BMJ Case Reports
William Pao, Chia-Huey Ooi, Fabian Birzele, Astrid Ruefli-Brasse, Michael A Cannarile, Bernhard Reis, Sebastian H Scharf, David A Schubert, Klas Hatje, Nadege Pelletier, Olivia Spleiss, John C Reed
Checkpoint inhibitor therapy has been a breakthrough in cancer research, but only some patients with cancer derive substantial benefit. Although mechanisms underlying sensitivity and resistance to checkpoint inhibitors are being elucidated, the importance of organ-specific regulation of immunity is currently underappreciated. Here, we call for a greater understanding of tissue-specific immunoregulation, namely, "tissue-specific immunostats," to make advances in treatments for cancer. A better understanding of how individual organs at baseline regulate the immune system could enable an improved precision medicine approach to cancer immunotherapy...
March 15, 2018: Cancer Discovery
Hamid Reza Mirzaei, Hossein Pourghadamyari, Majid Rahmati, Abbas Mohammadi, Javid Sadri Nahand, Abbas Rezaei, Hamed Mirzaei, Jamshid Hadjati
Recently clinical trials utilizing genetically engineered T cells expressing a chimeric antigen receptor (CAR) that is half monoclonal antibody and half T-cell receptor have demonstrated remarkable response in patients with advanced cancers like relapsed or refractory acute lymphoblastic leukemia (ALL) and lymphoma. Moreover, emerging chimeric genome editing tools such as zinc-finger nucleases (ZNFs), transcription activator-like effector nucleases (TALENs) and clustered regulatory interspaced short palindromic repeat (CRISPR)/Cas composed of sequence-specific DNA binding module(s) linked to a non-specific DNA cleavage domain have made possible to dramatically expand the ability to manipulate cells aim to treat and/or study a wide range of diseases including cancer...
March 12, 2018: Cancer Letters
Julia E Gerson, Kathleen M Farmer, Natalie Henson, Diana L Castillo-Carranza, Mariana Carretero Murillo, Urmi Sengupta, Alan Barrett, Rakez Kayed
BACKGROUND: We have evaluated the efficacy of targeting the toxic, oligomeric form of tau protein by passive immunotherapy in a mouse model of synucleinopathy. Parkinson's disease and Lewy body dementia are two of the most common neurodegenerative disorders and are primarily characterized by the accumulation of α-synuclein in Lewy bodies. However, evidence shows that smaller, oligomeric aggregates are likely the most toxic form of the protein. Moreover, a large body of research suggests that α-synuclein interacts with tau in disease and may act in a synergistic mechanism, implicating tau oligomers as a potential therapeutic target...
March 15, 2018: Molecular Neurodegeneration
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