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Specific immunotherapy

Nicole Groh, Christian Seutter von Loetzen, Brinda Subbarayal, Christian Möbs, Lothar Vogel, Andreas Hoffmann, Kay Fötisch, Anna Koutsouridou, Stefanie Randow, Elke Völker, Andreas Reuter, Paul Rösch, Stefan Vieths, Wolfgang Pfützner, Barbara Bohle, Dirk Schiller
BACKGROUND: Allergen-specific immunotherapy (AIT) with birch pollen generates Bet v 1-specific immunoglobulin (Ig)G4 which blocks IgE-mediated hypersensitivity mechanisms. Whether IgG4 specific for Bet v1a competes with IgE for identical epitopes or whether novel epitope specificities of IgG4 antibodies are developed is under debate. OBJECTIVE: We sought to analyze the epitope specificities of IgE and IgG4 antibodies from sera of patients who received AIT. METHODS: 15 sera of patients (13/15 received AIT) with Bet v 1a-specific IgE and IgG4 were analyzed...
October 22, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Liqing Wang, Suresh Kumar, Satinder Dahiya, Feng Wang, Jian Wu, Kheng Newick, Rongxiang Han, Arabinda Samanta, Ulf H Beier, Tatiana Akimova, Tricia R Bhatti, Benjamin Nicholson, Mathew P Kodrasov, Saket Agarwal, David E Sterner, Wei Gu, Joseph Weinstock, Tauseef R Butt, Steven M Albelda, Wayne W Hancock
Foxp3+ T-regulatory (Treg) cells are known to suppress protective host immune responses to a wide variety of solid tumors, but their therapeutic targeting is largely restricted to their transient depletion or "secondary" modulation, e.g. using anti-CTLA-4 monoclonal antibody. Our ongoing studies of the post-translational modifications that regulate Foxp3 demonstrated that the histone/protein acetyltransferase, Tip60, plays a dominant role in promoting acetylation, dimerization and function in Treg cells. We now show that the ubiquitin-specific protease, Usp7, controls Treg function largely by stabilizing the expression and promoting the multimerization of Tip60 and Foxp3...
October 15, 2016: EBioMedicine
J Chee, B W S R Robinson, R A Holt, J Creaney
Harnessing the immune system to fight cancer is an exciting advancement in lung cancer therapy. Anti-tumor immunity can be augmented by checkpoint blockade therapy, which removes the inhibition/brakes imposed on the immune system by the tumor. Checkpoint blockade therapy with anti-PD1/anti-PDL1 antibodies causes tumor regression in around 25% of lung cancer patients. In another approach, the immune system is forced or accelerated to attack the tumour, via augmentation of the anti-tumour response against mutations carried by each lung tumour...
October 18, 2016: Chest
S Sengupta, G Mao, Z S Gokaslan, P Sampath
Glioblastoma (GBM) is by far the most common and the most aggressive of all the primary brain malignancies. No curative therapy exists, and median life expectancy hovers at around 1 year after diagnosis, with a minute fraction surviving beyond 5 years. The difficulty in treating GBM lies in the cancer's protected niche within the blood-brain barrier and the heterogeneity of the cancer cells, which possess varying degrees of susceptibility to various common modalities of treatment. Over time, it is the tumor heterogeneity of GBM and the ability of the cancer stem cells to evolve in response treatment that renders the cancer refractory to conventional treatment...
October 21, 2016: Cancer Gene Therapy
B Rodríguez-Jiménez, E Muñoz-García, S Veza Perdomo, C González Herrada, C Kindelán-Recarte, J Domínguez-Ortega
No abstract text is available yet for this article.
October 2016: Journal of Investigational Allergology & Clinical Immunology
Peter Bailey, David K Chang, Marie-Andrée Forget, Francis A San Lucas, Hector A Alvarez, Cara Haymaker, Chandrani Chattopadhyay, Sun-Hee Kim, Suhendan Ekmekcioglu, Elizabeth A Grimm, Andrew V Biankin, Patrick Hwu, Anirban Maitra, Jason Roszik
Immunotherapy approaches for pancreatic ductal adenocarcinoma (PDAC) have met with limited success. It has been postulated that a low mutation load may lead to a paucity of T cells within the tumor microenvironment (TME). However, it is also possible that while neoantigens are present, an effective immune response cannot be generated due to an immune suppressive TME. To discern whether targetable neoantigens exist in PDAC, we performed a comprehensive study using genomic profiles of 221 PDAC cases extracted from public databases...
October 20, 2016: Scientific Reports
Marco Ruella, Marcela V Maus
Immunotherapy is the revolution in cancer treatment of this last decade. Among multiple approaches able to harness the power of the immune system against cancer, T cell based immunotherapies represent one of the most successful examples. In particular, biotechnological engineering of protein structures, like the T cell receptor or the immunoglobulins, allowed the generation of synthetic peptides like chimeric antigen receptors and bispecific antibodies that are able to redirect non-tumor specific T cells to recognize and kill leukemic cells...
2016: Computational and Structural Biotechnology Journal
Frederick J Kohlhapp, Erica J Huelsmann, Andrew T Lacek, Jason M Schenkel, Jevgenijs Lusciks, Joseph R Broucek, Josef W Goldufsky, Tasha Hughes, Janet P Zayas, Hubert Dolubizno, Ryan T Sowell, Regina Kühner, Sarah Burd, John C Kubasiak, Arman Nabatiyan, Sh'Rae Marshall, Praveen K Bommareddy, Shengguo Li, Jenna H Newman, Claude E Monken, Sasha H Shafikhani, Amanda L Marzo, Jose A Guevara-Patino, Ahmed Lasfar, Paul G Thomas, Edmund C Lattime, Howard L Kaufman, Andrew Zloza
In light of increased cancer prevalence and cancer-specific deaths in patients with infections, we investigated whether infections alter anti-tumor immune responses. We report that acute influenza infection of the lung promotes distal melanoma growth in the dermis and leads to accelerated cancer-specific host death. Furthermore, we show that during influenza infection, anti-melanoma CD8(+) T cells are shunted from the tumor to the infection site, where they express high levels of the inhibitory receptor programmed cell death protein 1 (PD-1)...
October 18, 2016: Cell Reports
Behjatolah Monzavi-Karbassi, Fariba Jousheghany, Thomas Kieber-Emmons
Development of cancer vaccines targeting tumor-associated antigens (TAAs) is an alternative approach to chemotherapy with sustained anti-tumor effects. The success of active immunotherapy has been hampered by tumor-induced immune suppressors. Regulatory T cells (Tregs) are a population of immune suppressors with a proven role in regulating anti-tumor immune responses. Removing or subduing Tregs activity leads to more robust anti-tumor immune responses. Here, we used a cell-based vaccination strategy in the 4T1 murine mammary model to examine whether bulk removal of certain TAAs, using their glycan profile, can affect the immunogenicity of the vaccine...
October 19, 2016: Immunological Investigations
Andrew Zloza, Neal D Dharmadhikari, Erica J Huelsmann, Joseph R Broucek, Tasha Hughes, Frederick J Kohlhapp, Howard L Kaufman
Recombinant interleukin-2 (rIL-2) is associated with objective responses in 15-20 % of patients with metastatic melanoma and renal cell carcinoma. More recently, rIL-2 has also demonstrated improved clinical activity in patients with melanoma. Given the toxicity of high-dose rIL-2 and the availability of many new immunotherapy agents, it has been suggested that lower doses of rIL-2 may be preferred for combination clinical studies. In order to determine the impact of low doses of rIL-2 on anti-tumor immunity and therapeutic effectiveness, we challenged C57BL/6 mice with poorly immunogenic B16-F10 melanoma and treated them with varying doses of rIL-2 (range 10(3)-10(5) IU)...
October 18, 2016: Cancer Immunology, Immunotherapy: CII
Sanne Duinkerken, Yvette van Kooyk, Juan J Garcia-Vallejo
Glioblastoma multiforme (GBM) is the most aggressive brain tumor and median survival time with current therapies is only 14.6 mo. Although multiple immunotherapeutic strategies are being explored, efficacy remains poor. In order to improve immunotherapy for GBM, we propose to combine currently used endogenous with human cytomegalovirus (HCMV) specific antigens expressed on cancer cells.
2016: Oncoimmunology
Sreya Bagchi, Sha Li, Chyung-Ru Wang
Adoptive immunotherapy for cancer treatment is an emerging field of study. Till now, several tumor-derived, peptide-specific T cell responses have been harnessed for treating cancers. However, the contribution of lipid-specific T cells in tumor immunity has been understudied. CD1 molecules, which present self- and foreign lipid antigens to T cells, are divided into group 1 (CD1a, CD1b, and CD1c) and group 2 (CD1d). Although the role of CD1d-restricted natural killer T cells (NKT) in several tumor models has been well established, the contribution of group 1 CD1-restricted T cells in tumor immunity remains obscure due to the lack of group 1 CD1 expression in mice...
2016: Oncoimmunology
Leonid Dubrovsky, Elliott Joseph Brea, Dmitry Pankov, Emily Casey, Tao Dao, Cheng Liu, David A Scheinberg
Specific immunotherapy for acute leukemia remains a great unmet need. Native unmodified monoclonal antibody therapies, while promising, are inadequately effective for these malignancies, and multiple mechanisms for failure have been described. Antibody-dependent cellular cytotoxicity or phagocytosis is the primary modality of mAb-mediated cell killing in vivo, but ultimately leads to relapse of the leukemias, in model systems and in humans. By use of a T-cell receptor mimic mAb ESKM, derived against a WT1 peptide expressed in complex with HLA-A*02:01, whose only mechanism of therapeutic action is ADCC, we evaluated the mechanisms of leukemic relapse from its potent therapeutic action in mouse xenograft models of human leukemia...
2016: Oncoimmunology
Xuhao Zhang, Shan Zhu, Tete Li, Yong-Jun Liu, Wei Chen, Jingtao Chen
Malignant glioma is the most common and a highly aggressive cancer in the central nervous system (CNS). Cancer immunotherapy, strategies to boost the body's anti-cancer immune responses instead of directly targeting tumor cells, recently achieved great success in treating several human solid tumors. Although once considered "immune privileged" and devoid of normal immunological functions, CNS is now considered a promising target for cancer immunotherapy, featuring the recent progresses in neurobiology and neuroimmunology and a highly immunosuppressive state in malignant glioma...
October 16, 2016: Oncotarget
N R Datta, S Krishnan, D E Speiser, E Neufeld, N Kuster, S Bodis, H Hofmann
Effective multimodal cancer management requires the optimal integration of diagnostic and therapeutic modalities. Radiation therapy, chemotherapy and immunotherapy, alone or in combination, are integral parts of various cancer treatment protocols. Hyperthermia at 39-45°C is a potent radiosensitiser and has been shown to improve therapeutic outcomes in various tumours through its synergy with chemotherapy. Gene silencing approaches, using small interfering RNAs and microRNAs, are also being explored in clinical trials in oncology...
October 3, 2016: Cancer Treatment Reviews
Yi Zheng, Yicheng Yang, Shu Wu, Yongqiang Zhu, Xiaolong Tang, Xiaopeng Liu
As the second most common gynecologic malignant tumors with a high mortality rate, cervical cancer jeopardizes women's life worldwide. The low cure rate in cervical cancer patients is mainly attributed to the lack of effective therapies. One feasible novel strategy is to develop immune-based approaches such as adoptive cell immunotherapy of DCCIKs which represents a promising nontoxic antineoplastic immunotherapy preferred in clinic practice. However, the therapeutic effect is not as efficient as anticipated...
October 18, 2016: Bioengineered
Sandra Cascio, Olivera J Finn
Altered glycosylation of mucin 1 (MUC1) on tumor cells compared to normal epithelial cells was previously identified as an important antigenic modification recognized by the immune system in the process of tumor immunosurveillance. This tumor form of MUC1 is considered a viable target for cancer immunotherapy. The importance of altered MUC1 glycosylation extends also to its role as a promoter of chronic inflammatory conditions that lead to malignant transformation and cancer progression. We review here what is known about the role of specific cancer-associated glycans on MUC1 in protein-protein interactions and intracellular signaling in cancer cells and in their adhesion to each other and the tumor stroma...
October 13, 2016: Biomolecules
Shih-Ping Cheng, Po-Sheng Yang, Ming-Nan Chien, Ming-Jen Chen, Jie-Jen Lee, Chien-Liang Liu
BACKGROUND AND OBJECTIVES: The induction of tumor-associated carbohydrate antigen results from altered glycosylation in transformed cells. Globo H is a hexasaccharide glycosphingolipid overexpressed on malignancies of epithelial origin and has become an attractive vaccine target. We aimed to investigate the expression patterns and prognostic value of Globo H in thyroid neoplasms. METHODS: Globo H expression was examined by immunohistochemical analysis using commercial and in-house tissue microarrays...
October 18, 2016: Journal of Surgical Oncology
Laura C Cappelli, Ami A Shah, Clifton O Bingham
Immune checkpoint inhibitors (ICIs) are newly approved treatments for advanced malignancies that are increasing survival. The mechanism of these drugs, non-specifically activating T cells, also leads to immune-mediated damage of tissue or immune-related adverse events (IRAE). IRAEs with rheumatic phenotypes are increasingly being recognised. Inflammatory arthritis, sicca syndrome, inflammatory myopathy, vasculitis and lupus nephritis have been described as a result of ICIs. Use of ICIs will be expanding in the coming years for several reasons...
2016: RMD Open
Peter Sidaway
No abstract text is available yet for this article.
October 18, 2016: Nature Reviews. Clinical Oncology
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