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Subcutaneous immunotherapy

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
Xuandao Liu, Chew Lip Ng, De Yun Wang
Sublingual immunotherapy (SLIT) has been proven to be safe and effective from an abundance of Western literature, but data from Asia is less complete. This review aims to examine the basic science, safety and efficacy of SLIT in Asian patients, and to determine future research needs in Asia. We performed a literature search on PUBMED, Scopus, and Cochrane Library database for articles on SLIT originating from Asian countries through Nov 2017. There were 18 randomized, double-blind, placebo-controlled trials, of which 9 involved solely paediatric subjects...
March 15, 2018: Allergology International: Official Journal of the Japanese Society of Allergology
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
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
Adriano Luís Soares De Souza, Stefan Rudin, Rui Chang, Keith Mitchell, Timothy Crandall, Shuning Huang, Ji-Kyung Choi, Shinji L Okitsu, Danielle L Graham, Blake Tomkinson, Tammy Dellovade
INTRODUCTION: Antigen-specific immunotherapy could provide a targeted approach for the treatment of multiple sclerosis that removes the need for broad-acting immunomodulatory drugs. ATX-MS-1467 is a mixture of four peptides identified as the main immune-dominant disease-associated T-cell epitopes in myelin basic protein (MBP), an autoimmune target for activated autoreactive T cells in multiple sclerosis. Previous animal studies have shown that ATX-MS-1467 treatment prevented the worsening of signs of disease in experimental autoimmune encephalitis (EAE) in the humanized (DR2 × Ob1)F1 mouse in a dose-dependent fashion...
March 14, 2018: Neurology and Therapy
Matteo Ferrando, Francesca Racca, Lorena Nascimento Girardi Madeira, Enrico Heffler, Giovanni Passalacqua, Francesca Puggioni, Niccolò Stomeo, Giorgio Walter Canonica
Abstract: Allergen immunotherapy (AIT) is the only disease-modifying treatment approved for allergic rhinitis and allergic asthma and represents a suitable therapeutic option, especially in childhood, to modify the progression of respiratory allergic diseases. Starting from the previous "generic class effect" evaluation, as testified by the numerous meta analyses, AIT is now considered a product-specific pathogenic-oriented treatment. Background: AIT was empirically proposed more than one century ago in the subcutaneous form (SCIT), but the IgE-mediated mechanism of allergy was elucidated only after 50 years of clinical use of the treatment...
2018: Clinical and Molecular Allergy: CMA
Min Zhou, Xinjian Liu, Zonghai Li, Qian Huang, Fang Li, Chuan-Yuan Li
Caspase-3 (CASP3) is a major mediator of apoptosis activated during cellular exposure to cytotoxic drugs, radiotherapy, or immunotherapy. It is often used as a marker for efficacy of cancer therapy. However, recent reports indicate that caspase-3 also has non-apoptotic roles such as promotion of tumor relapse and tumor angiogenesis. Therefore, the roles of caspase-3 in tumor progression remains to be defined clearly. In this study, we established caspase-3 knockout (KO) colon cancer cell lines by use of the CRISPR technology...
March 10, 2018: International Journal of Cancer. Journal International du Cancer
Ralph Mösges, Claus Bachert, Petr Panzner, Moises A Calderon, Ludo Haazen, Sabine Pirotton, Nathalie Wathelet, Stephen R Durham, Marie-Alix Bonny, Thierry Legon, Remy von Frenckell, Oliver Pfaar, Mohamed H Shamji
BACKGROUND: Immunotherapy with peptide hydrolysates from Lolium perenne (LPP) is an alternative treatment for seasonal allergic rhinitis with or without asthma. The aim of this study was to assess the clinical efficacy and safety of a cumulative dose of 170 μg LPP administered subcutaneously over 3 weeks. METHODS: In a randomized, double blind, placebo-controlled trial, 554 adults with grass pollen rhinoconjunctivitis were randomized (1:2 ratio) to receive 8 subcutaneous injections of placebo or 170 μg LPP administered in increasing doses in 4 visits over 3 weeks...
March 7, 2018: Allergy
Connie B Gilfillan, Sabine Kuhn, Camille Baey, Evelyn J Hyde, Jianping Yang, Christiane Ruedl, Franca Ronchese
In the steady state, tumors harbor several populations of dendritic cells (DCs) and myeloid cells that are key regulators of the intratumoral immune environment. Among these cells, migratory CD103+ cross-presenting DCs are thought to be critical for tumor-specific CTL responses and tumor resistance. However, it is unclear whether this prominent role also extends to immunotherapy. We used a murine orthotopic mammary tumor model, as well as Clec9A-diphtheria toxin receptor mice that can be depleted of the specialized cross-presenting CD8α+ and CD103+ DC1 subsets, to investigate the role of these DCs in immunotherapy...
March 5, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Deniz Genç, Noushin Zibandeh, Ercan Nain, Muazzez Gökalp, Ahmet Oğuzhan Özen, Mehmet Kamil Göker, Tunç Akkoç
BACKGROUND: Asthma is a chronic inflammatory disease in which inflammatory responses have the polarization of CD4+ T cells to Th2 cells. Dental follicle mesenchymal stem cells (DFSCs) have strong anti-inflammatory properties comparable to other mesenchymal stem cells. OBJECTIVE: We investigated the immunomodulatory effects of DFSCs on CD4+ T helper cell responses of asthmatic patients and compared the results with those obtained with asthmatic subjects on immunotherapy and with healthy individuals...
March 2, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Bernhard Michalke, Matthias F Kramer, Randolf Brehler
BACKGROUND: Aluminium is associated with disorders and is the commonly used vaccine adjuvant. Understanding the mechanisms of how Al is transported, metabolized or of its toxicity depends on the knowledge of Al-interactions with bioligands, i.e. Al-species. Al-speciation in serum is difficult because of low concentration and the risk of exogenous Al contamination. Furthermore, Al-measurements may be hampered according to various interferences. This study aims for developing quality controlled protocols for reliable Al- and Al-species determination and for investigating probable differences in Al (-speciation) after Al-containing subcutaneous immunotherapy (SIT)...
February 21, 2018: Journal of Trace Elements in Medicine and Biology
Rui Kuai, Xiaoqi Sun, Wenmin Yuan, Yao Xu, Anna Schwendeman, James J Moon
While cancer immunotherapy provides new exciting treatment options for patients, there is an urgent need for new strategies that can synergize with immune checkpoint blockers and boost the patient response rates. We have developed a personalized vaccine nanodisc platform based on synthetic high-density lipoproteins for co-delivery of immunostimulatory agents and tumor antigens, including tumor-specific neoantigens. Here we examined the route of delivery, safety profiles, and therapeutic efficacy of nanodisc vaccination against established tumors...
February 27, 2018: Bioconjugate Chemistry
Yu Shao, Zhan-Yi Sun, Yijie Wang, Bo-Dou Zhang, Dongsheng Liu, Yan-Mei Li
Immunotherapy is believed to be an ideal method to treat cancer because it can break the immunotolerance of tumor and induce robust immunoresponse. However, constructing a wide antigen-adaptive, easy-handling, biodegradable system that can recruit and activate APCs much effectively is still a challenge. Herein, we show that an injectable DNA supramolecular hydrogel vaccine (DSHV) system which could efficiently recruit and activate APCs in vitro and in vivo. The in vitro processes have been visualized by fluorescence microscopy...
February 27, 2018: ACS Applied Materials & Interfaces
Hyunjoon Kim, Lin Niu, Peter Larson, Tamara A Kucaba, Katherine A Murphy, Britnie R James, David M Ferguson, Thomas S Griffith, Jayanth Panyam
Cytotoxic T lymphocytes (CTLs) play a major role in cancer immunotherapy because of their ability to directly kill tumor cells and secrete tumor suppressive cytokines. Anticancer vaccines aim to provoke tumor-specific CTL responses, which require activation of antigen presenting cells (APCs) including dendritic cells (DCs) and macrophages. Therefore, a potent immunostimulatory adjuvant capable of activating APCs is an essential component of anticancer vaccines. In this study, we introduce novel TLR 7/8 bi-specific agonists that significantly enhance cytokine secretion compared to TLR7 mono-selective compounds...
February 17, 2018: Biomaterials
Jeremy Chataway, Keith Martin, Kevin Barrell, Basil Sharrack, Pelle Stolt, David C Wraith
OBJECTIVE: To assess safety, tolerability, and efficacy of the antigen-specific immunotherapy ATX-MS-1467 in participants with relapsing multiple sclerosis using different treatment protocols to induce tolerance. METHODS: Two open-label trials in adult participants with relapsing multiple sclerosis were conducted. Study 1 was a multicenter, phase 1b safety evaluation comparing intradermal (i.d.) (cohort 1) with subcutaneous (cohort 2) administration in 43 participants...
February 21, 2018: Neurology
Arsalan Alizadeh, Kallivalappil T Santhosh, Hardeep Kataria, Abdelilah S Gounni, Soheila Karimi-Abdolrezaee
BACKGROUND: Spinal cord injury (SCI) triggers a robust neuroinflammatory response that governs secondary injury mechanisms with both degenerative and pro-regenerative effects. Identifying new immunomodulatory therapies to promote the supportive aspect of immune response is critically needed for the treatment of SCI. We previously demonstrated that SCI results in acute and permanent depletion of the neuronally derived Neuregulin-1 (Nrg-1) in the spinal cord. Increasing the dysregulated level of Nrg-1 through acute intrathecal Nrg-1 treatment enhanced endogenous cell replacement and promoted white matter preservation and functional recovery in rat SCI...
February 21, 2018: Journal of Neuroinflammation
Lukasz Bialkowski, Kevin Van der Jeught, Sanne Bevers, Patrick Tjok Joe, Dries Renmans, Carlo Heirman, Joeri L Aerts, Kris Thielemans
Improved understanding of cancer immunology has provided insight into the phenomenon of frequent tumor recurrence after initially successful immunotherapy. A delicate balance exists between the capacity of the immune system to control tumor growth and various resistance mechanisms that arise to avoid or even counteract the host's immune system. These resistance mechanisms include, but are not limited to (1) adaptive expression of inhibitory checkpoint molecules in response to the pro-inflammatory environment and (2) amplification of cancer stem cells, a small fraction of tumor cells possessing the capacity for self-renewal and mediating treatment resistance and formation of metastases after long periods of clinical remission...
February 21, 2018: International Journal of Cancer. Journal International du Cancer
Rizwan Romee, Sarah Cooley, Melissa M Berrien-Elliott, Peter Westervelt, Michael R Verneris, John E Wagner, Daniel J Weisdorf, Bruce R Blazar, Celalettin Ustun, Todd E DeFor, Sithara Vivek, Lindsey Peck, John F DiPersio, Amanda F Cashen, Rachel Kyllo, Amy Musiek, András Schaffer, Milan J Anadkat, Ilana Rosman, Daniel Miller, Jack O Egan, Emily K Jeng, Amy Rock, Hing C Wong, Todd A Fehniger, Jeffrey S Miller
New therapies for patients with hematologic malignancies who relapse after allogeneic hematopoietic cell transplantation (allo-HCT) are needed. Interleukin (IL)-15 is a cytokine that stimulates CD8+ T cell and NK cell anti-tumor responses, and we hypothesized this cytokine may augment anti-leukemia/lymphoma immunity in vivo. To test this, we performed a first-in-human multi-center phase 1 trial ( NCT01885897) of the IL-15 superagonist complex ALT-803 in patients who relapsed >60 days after allo-HCT...
February 20, 2018: Blood
David G Leach, Neeraja Dharmaraj, Stacey L Piotrowski, Tania L Lopez-Silva, Yu L Lei, Andrew G Sikora, Simon Young, Jeffrey D Hartgerink
Recent advancements in the field of immunotherapy have yielded encouraging results for the treatment of advanced cancers. Cyclic dinucleotides (CDNs) are a powerful new class of immunotherapy drugs known as STING (Stimulator of Interferon Genes) agonists, currently in clinical trials. However, previous studies of CDNs in murine cancer models have required multiple injections, and improve survival only in relatively nonaggressive tumor models. Therefore, we sought to improve the efficacy of CDN immunotherapy by developing a novel biomaterial we call "STINGel...
February 6, 2018: Biomaterials
Lin Yu, Ying Lu, Yuqin Yao, Yu Liu, Yuxi Wang, Qinhuai Lai, Ruirui Zhang, Wenting Li, Ruixue Wang, Yuyin Fu, Yiran Tao, Shuli Yi, Lantu Gou, Ligong Chen, Jinliang Yang
Small cell lung cancer (SCLC) is of a highly invasive and metastatic lung cancer subtype and there had not been effective targeted therapies. CD56, a cell surface marker highly expressed on most SCLC, is a promising therapeutic target for treatment of this aggressive cancer. In this study, we generated a novel anti-CD56 antibody named promiximab, characterized by high affinity, internalization and tumor specificity. Then, the promiximab was conjugated with a potent DNA alkylating agent duocarmycin via reduced interchain disulfides to yield the promiximab-Duocarmycin (promiximab-DUBA) conjugates...
January 12, 2018: Oncotarget
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