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https://www.readbyqxmd.com/read/28718965/long-term-effects-galectin-1-and-specific-immunotherapy-for-allergic-responses-in-the-intestine
#1
Li-Tao Yang, Qing Shu, Xiang-Qian Luo, Zhi-Qiang Liu, Shu-Qi Qiu, Jiang-Qi Liu, Hai-Jian Guo, Lin-Jing Li, Mao-Gang Li, Da-Bo Liu, Li-Xin Xia, Zhi-Gang Liu, Ping-Chang Yang
BACKGROUND AND AIMS: Mast cell activation interferes with the effects of allergen-specific immunotherapy (SIT). Galectin-1 (Gal-1) is capable of regulating immune cells' functions. This study tests the hypothesis that administration of Gal-1 promotes and prolongs the efficacy of SIT via suppressing mast cell activation. METHODS: An intestinal allergy mouse model was developed. The co-administration of SIT and Gal-1 on suppression of the allergic responses, prevention of mast cell activation, and generation of antigen-specific regulatory T cells (Treg) in the intestine were observed in sensitized mice...
July 18, 2017: Allergy
https://www.readbyqxmd.com/read/28718953/computational-validation-of-the-recently-proposed-pollen-season-definition-criteria
#2
K Karatzas, M Riga, U Berger, M Werchan, O Pfaar, K Ch Bergmann
In a recently published paper (Pfaar et al., 2016), a Task Force of the Immunotherapy and Aerobiology and Pollution Interest Groups of the EAACI suggested specific criteria for the definition of pollen exposure times for three types of pollen events: (a) Pollen Season (PS) start and end, (b) high pollen season (or Peak Pollen Period-PPP) start and end, and (c) high pollen days. Species addressed included Birch, Grasses, Cypress, Olive, and Ragweed. Two important questions arise from the aforementioned definitions: (i) do they lead to a narrow (thus well defined) time interval identifying start and end event dates (robustness of the criteria) and (ii) if slightly altered, will they result to a narrow (thus again well defined) fluctuation of start and end event dates (sensitivity of the criteria)? In an effort to provide with responses to aforementioned questions, we analyzed Poaceae pollen count data coming from Germany (up to 40 pollen monitoring stations, years 2012-2016)...
July 18, 2017: Allergy
https://www.readbyqxmd.com/read/28718815/regional-delivery-of-chimeric-antigen-receptor-car-t-cells-for-cancer-therapy
#3
REVIEW
Praveen Sridhar, Fabio Petrocca
Chimeric Antigen Receptor (CAR) T-cells are T-cells with recombinant receptors targeted to tumor antigens. CAR-T cell therapy has emerged as a mode of immunotherapy and is now being extensively explored in hematologic cancer. In contrast, CAR-T cell use in solid tumors has been hampered by multiple obstacles. Several approaches have been taken to circumvent these obstacles, including the regional delivery of CAR-T cells. Regional CAR-T cell delivery can theoretically compensate for poor T-cell trafficking and tumor antigen specificity while avoiding systemic toxicity associated with intravenous delivery...
July 18, 2017: Cancers
https://www.readbyqxmd.com/read/28718424/targeted-therapy-and-immunosuppression-in-the-tumor-microenvironment
#4
REVIEW
Michael J Allegrezza, Jose R Conejo-Garcia
Small-molecule inhibitors offer great promise for targeting pathways that are specifically deregulated in different tumors. However, such 'targeted' therapies also elicit poorly understood effects on protective antitumor immunity. Given the emerging relevance of immunotherapies that boost pre-existing T cell responses, understanding how different immune cells are affected by small-molecule inhibitors could lead to more-effective interventions, alone or combined with immunotherapy. This review discusses the growing array of activities elicited by multiple 'targeted' inhibitors on antitumor immunity, underscoring the complex effects resulting from diverse activities on different immune cell types in vivo, and the need to conduct mechanistic research that identifies drugs performing well not only in immunocompromised mice but also in the presence of spontaneous or therapeutic antitumor immunity...
January 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28717940/alopecia-areata-a-comprehensive-review-of-pathogenesis-and-management
#5
REVIEW
Ralph M Trüeb, Maria Fernanda Reis Gavazzoni Dias
Alopecia areata is a common hair loss condition that is characterized by acute onset of non-scarring hair loss in usually sharply defined areas ranging from small patches to extensive or less frequently diffuse involvement. Depending on its acuity and extent, hair loss is an important cause of anxiety and disability. The current understanding is that the condition represents an organ-specific autoimmune disease of the hair follicle with a genetic background. Genome-wide association studies provide evidence for the involvement of both innate and acquired immunity in the pathogenesis, and mechanistic studies in mouse models of alopecia areata have specifically implicated an IFN-γ-driven immune response, including IFNγ, IFNγ-induced chemokines and cytotoxic CD8 T cells as the main drivers of disease pathogenesis...
July 17, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28717398/preclinical-evaluation-of-nf-%C3%AE%C2%BAb-triggered-dendritic-cells-expressing-the-viral-oncogenic-driver-of-merkel-cell-carcinoma-for-therapeutic-vaccination
#6
Kerstin F Gerer, Michael Erdmann, Sine R Hadrup, Rikke Lyngaa, Lena-Marie Martin, Reinhard E Voll, Beatrice Schuler-Thurner, Gerold Schuler, Niels Schaft, Stefanie Hoyer, Jan Dörrie
BACKGROUND: Merkel cell carcinoma (MCC) is a rare but very aggressive skin tumor that develops after integration of a truncated form of the large T-antigen (truncLT) of the Merkel cell polyomavirus (MCV) into the host's genome. Therapeutic vaccination with dendritic cells (DCs) loaded with tumor antigens is an active form of immunotherapy, which intends to direct the immune system towards tumors which express the respective vaccination antigens. METHODS: Cytokine-matured monocyte-derived DCs of healthy donors and MCC patients were electroporated with mRNA encoding the truncLT...
July 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28716899/hdac1-upregulation-by-nanog-promotes-multidrug-resistance-and-a-stem-like-phenotype-in-immune-edited-tumor-cells
#7
Kwon-Ho Song, Chel Hun Choi, Hyo-Jung Lee, Se Jin Oh, Seon Rang Woo, Soon-Oh Hong, Kyung Hee Noh, Hanbyoul Cho, Eun Joo Chung, Jae-Hoon Kim, Joon-Yong Chung, Stephen M Hewitt, Seungki Baek, Kyung-Mi Lee, Cassian Yee, Minjoo Son, Chih-Ping Mao, T-C Wu, Tae Woo Kim
Cancer immunoediting drives the adaptation of tumor cells to host immune surveillance. Immunoediting driven by antigen (Ag)-specific T cells enriches NANOG expression in tumor cells, resulting in a stem-like phenotype and immune resistance. Here we identify HDAC1 as a key mediator of the NANOG-associated phenotype. NANOG upregulated HDAC1 through promoter occupancy, thereby decreasing histone H3 acetylation on K14 and K27. NANOG-dependent, HDAC1-driven epigenetic silencing of cell cycle inhibitor CDKN2D and CDKN1B induced stem-like features...
July 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28716814/potency-matched-dual-cytokine-antibody-fusion-proteins-for-cancer-therapy
#8
Roberto De Luca, Alex Soltermann, Francesca Pretto, Catherine Pemberton-Ross, Giovanni Pellegrini, Sarah Wulhfard, Dario Neri
A novel biopharmaceutical, consisting of the F8 monoclonal antibody (specific to a splice isoform of fibronectin) simultaneously fused to both tumor necrosis factor and interleukin-2, was found to react with the majority of solid tumors and hematological malignancies in mouse and man, but not with healthy adult tissues. The product selectively localized to neoplastic lesions in vivo, as evidenced by quantitative biodistribution studies using radioiodinated protein preparations. When the potency of the cytokine payloads was matched by a single-point mutation, the resulting fusion protein (IL2-F8-TNF(mut)) eradicated soft-tissue sarcomas in immunocompetent mice, which did not respond to individual antibody-cytokine fusion proteins or by standard doxorubicin treatment...
July 17, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28716652/toxicity-profiles-of-immunotherapy
#9
REVIEW
Sophie Cousin, Antoine Italiano
Immunotherapies are changing the landscape of advanced solid tumor treatment. These therapies have different mechanisms of action and include oncolytic viruses, checkpoint inhibitors, such as CTLA-4 or PD1/PD-L1 monoclonal antibodies, and CSF-1R antibodies. Given the growing therapeutic impact of these agents in oncology, it is important to better understand their properties. Immunotherapies generate new toxicity profiles that are called immune-related adverse events and require specific management. This review focuses on the mechanisms of action of such side effects, as well as their description and their general management...
July 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28716155/transplanters-drive-cars-to-the-clinic-by-brewing-ice-t-the-moffitt-roadmap
#10
EDITORIAL
Frederick L Locke, Claudio Anasetti
Recent single institution clinical trial successes with anti-CD19 Chimeric Antigen Receptor (CAR) T cell therapy for B cell malignancies attracted significant attention from industry. Our center sought to rapidly and safely bring industry sponsored pivotal trials to our patients and to prepare for additional cell therapy trials in solid and liquid tumors from both industry and our own investigators. We implemented a collaborative cross departmental program to provide clinical care and trial coordination for immune cell therapies...
July 18, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28716080/pretreatment-antigen-specific-immunity-and-regulation-association-with-subsequent-immune-response-to-anti-tumor-dna-vaccination
#11
Laura E Johnson, Brian M Olson, Douglas G McNeel
BACKGROUND: Immunotherapies have demonstrated clinical benefit for many types of cancers, however many patients do not respond, and treatment-related adverse effects can be severe. Hence many efforts are underway to identify treatment predictive biomarkers. We have reported the results of two phase I trials using a DNA vaccine encoding prostatic acid phosphatase (PAP) in patients with biochemically recurrent prostate cancer. In both trials, persistent PAP-specific Th1 immunity developed in some patients, and this was associated with favorable changes in serum PSA kinetics...
July 18, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28716061/colony-stimulating-factor-1-receptor-csf1r-inhibitors-in-cancer-therapy
#12
REVIEW
Michael A Cannarile, Martin Weisser, Wolfgang Jacob, Anna-Maria Jegg, Carola H Ries, Dominik Rüttinger
The tumor-permissive and immunosuppressive characteristics of tumor-associated macrophages (TAM) have fueled interest in therapeutically targeting these cells. In this context, the colony-stimulating factor 1 (CSF1)/colony-stimulating factor 1 receptor (CSF1R) axis has gained the most attention, and various approaches targeting either the ligands or the receptor are currently in clinical development. Emerging data on the tolerability of CSF1/CSF1R-targeting agents suggest a favorable safety profile, making them attractive combination partners for both standard treatment modalities and immunotherapeutic agents...
July 18, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28715249/durable-molecular-remissions-in-chronic-lymphocytic-leukemia-treated-with-cd19-specific-chimeric-antigen-receptor-modified-t-cells-after-failure-of-ibrutinib
#13
Cameron J Turtle, Kevin A Hay, Laïla-Aïcha Hanafi, Daniel Li, Sindhu Cherian, Xueyan Chen, Brent Wood, Arletta Lozanski, John C Byrd, Shelly Heimfeld, Stanley R Riddell, David G Maloney
Purpose We evaluated the safety and feasibility of anti-CD19 chimeric antigen receptor-modified T (CAR-T) cell therapy in patients with chronic lymphocytic leukemia (CLL) who had previously received ibrutinib. Methods Twenty-four patients with CLL received lymphodepleting chemotherapy and anti-CD19 CAR-T cells at one of three dose levels (2 × 10(5), 2 × 10(6), or 2 × 10(7) CAR-T cells/kg). Nineteen patients experienced disease progression while receiving ibrutinib, three were ibrutinib intolerant, and two did not experience progression while receiving ibrutinib...
July 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28714940/non-coding-rnas-as-predictive-biomarkers-to-current-treatment-in-metastatic-colorectal-cancer
#14
REVIEW
Ingrid Garajová, Manuela Ferracin, Elisa Porcellini, Andrea Palloni, Francesca Abbati, Guido Biasco, Giovanni Brandi
The onset and selection of resistant clones during cancer treatment with chemotherapy or targeted therapy is a major issue in the clinical management of metastatic colorectal cancer patients. It is possible that a more personalized treatment selection, using reliable response-to-therapy predictive biomarkers, could lead to an improvement in the success rate of the proposed therapies. Although the process of biomarker selection and validation could be a long one, requiring solid statistics, large cohorts and multicentric validations, non-coding RNAs (ncRNAs) and in particular microRNAs, proved to be extremely promising in this field...
July 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28714919/overcoming-oncogenic-mediated-tumor-immunity-in-prostate-cancer
#15
REVIEW
Geoffrey Bryant, Lin Wang, David J Mulholland
Immunotherapy is being tested intensively in clinical trials for prostate cancer; it includes immune checkpoint inhibition, prostate specific antigen (PSA) vaccines and dendritic cell-based strategies. Despite increasing evidence for clinical responses, the consensus of multiple trials is that prostate cancers are poorly responsive to immunotherapy. Prostate cancer has a high degree of pathological and genetic heterogeneity compared to other cancer types, which may account for immunotherapeutic resistance. This hypothesis also implies that select types of prostate tumors may be differentially responsive to immune-based strategies and that the clinical stage, pathological grade and underlying genetic landscape may be important criteria in identifying tumors that respond to immune therapies...
July 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28714508/gold-glyconanoparticles-coupled-to-listeriolysin-o-91-99-peptide-serve-as-adjuvant-therapy-against-melanoma
#16
R Calderon-Gonzalez, H Terán-Navarro, I García, M Marradi, D Salcines-Cuevas, S Yañez-Diaz, A Solis-Angulo, E Frande-Cabanes, M C Fariñas, A Garcia-Castaño, J Gomez-Roman, S Penades, F Rivera, J Freire, C Álvarez-Domínguez
Dendritic cell-based (DC-based) vaccines are promising immunotherapies for cancer. However, several factors, such as the lack of efficient targeted delivery and the sources and types of DCs, have limited the efficacy of DCs and their clinical potential. We propose an alternative nanotechnology-based vaccine platform with antibacterial prophylactic abilities that uses gold glyconanoparticles coupled to listeriolysin O 91-99 peptide (GNP-LLO91-99), which acts as a novel adjuvant for cancer therapy. GNP-LLO91-99, when used to vaccinate mice, exhibited dual antitumour activities, namely, the inhibition of tumour migration and growth and adjuvant activity for recruiting and activating DCs, including those from melanoma patients...
July 17, 2017: Nanoscale
https://www.readbyqxmd.com/read/28714406/role-of-the-immune-component-of-tumor-microenvironment-in-the-efficiency-of-cancer-treatment-perspectives-for-the-personalized-therapy
#17
Marina Stakheyeva, Vladimir Riabov, Irina Mitrofanova, Nikolai Litviakov, Evgeny Choynzonov, Nadezhda Cherdyntseva, Julia Kzhyshkowska
Despite significant progress in cancer diagnostics and development of novel therapeutic regimens, successful treatment of advanced forms of cancer is still a challenge and may require personalized therapeutic approaches. In this review, we analyzed major mechanisms responsible for tumor cells chemoresistance and emphasized that intratumor heterogeneity is a critical factor that limits efficiency of cancer treatment. Intratumor heterogeneity is caused by genomic instability in cancer cells, resulting in the selection of resistant clones...
July 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28714192/secreted-tumor-antigens-immune-biomarkers-for-diagnosis-and-therapy
#18
REVIEW
Els N Meeusen, Elgene Lim, Suresh Mathivanan
With the advent of immunotherapies for cancer, there is growing interest in the identification of tumor antigens. Tumor antigens are self-molecules altered through genetic mutations (neoantigens), protein truncation, protein misfolding or abnormal post translational modifications. To induce an immune response, tumor antigens need to be secreted into the tumor environment and presented to the immune system in the draining lymph nodes, resulting in the generation of tumor-specific effector cells and antibodies...
July 17, 2017: Proteomics
https://www.readbyqxmd.com/read/28713677/radio-immunotherapy-and-chemo-immunotherapy-as-a-novel-treatment-paradigm-in-malignant-pleural-mesothelioma
#19
REVIEW
Licun Wu, Marc de Perrot
Malignant pleural mesothelioma (MPM) is an aggressive neoplasm with poor outcome. Novel radical radiation techniques using intensity modulated radiation therapy (IMRT) have become an important component of therapy in mesothelioma. Immunotherapy also provides new therapeutic options. However, how best to integrate immunotherapy with standard therapy such as radiation, chemotherapy and surgery remains unknown. A change of paradigm from adjuvant normofractionation to induction accelerated hypofractionated hemithoracic radiation could provide a platform to combine immunotherapy due to the potential benefit of short course high dose radiation on the immune system...
June 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28713676/immunotherapy-for-malignant-pleural-mesothelioma-current-status-and-future-directions
#20
REVIEW
Jordan Dozier, Hua Zheng, Prasad S Adusumilli
Malignant pleural mesothelioma (MPM) has been marked historically by poor prognosis. Current standard of care for this deadly disease results in sub-optimal improvements in overall survival (OS), which has prompted researchers to explore innovative treatment alternatives. Immunotherapy is an emerging therapeutic modality that harnesses the power of the human immune system. In this review, we summarize the different methods of immunotherapy for malignant pleural mesothelioma. Using ClinicalTrials.gov we searched the terms "immunotherapy" and "immune therapy" combined with "pleural mesothelioma"...
June 2017: Translational Lung Cancer Research
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