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https://www.readbyqxmd.com/read/29779209/gata3-hypermethylation-and-foxp3-hypomethylation-are-associated-with-sustained-protection-and-bystander-effect-following-epicutaneous-immunotherapy-in-peanut-sensitized-mice
#1
Lucie Mondoulet, Vincent Dioszeghy, Florence Busato, Camille Plaquet, Véronique Dhelft, Kevin Bethune, Laurence Leclere, Christian Daviaud, Mélanie Ligouis, Hugh Sampson, Christophe Dupont, Jörg Tost
BACKGROUND: Epicutaneous immunotherapy (EPIT) is a promising method for treating food allergies. In animal models, EPIT induces sustained unresponsiveness and prevents further sensitization mediated by Tregs. Here, we elucidate the mechanisms underlying the therapeutic effect of EPIT, by characterizing the kinetics of DNA methylation changes in sorted cells from spleen and blood and by evaluating its persistence and bystander effect compared to oral immunotherapy (OIT). METHODS: BALB/c mice orally sensitized to peanut proteins (PPE) were treated by EPIT using a PPE-patch or by PPE-OIT...
May 19, 2018: Allergy
https://www.readbyqxmd.com/read/29777794/regulatory-t-cell-targeted-hybrid-nanoparticles-combined-with-immuno-checkpoint-blockage-for-cancer-immunotherapy
#2
Wenquan Ou, Raj Kumar Thapa, Liyuan Jiang, Soe Zar Chi, Milan Gautam, Jae-Hoon Chang, Jee-Heon Jeong, Sae Kwang Ku, Han-Gon Choi, Chul Soon Yong, Jong Oh Kim
Immunosuppression in tumor microenvironments induced by regulatory T (Treg) cells is regarded a critical mechanism of tumor immune escape and poses a major impediment to cancer immunotherapy. In this study, we developed tLyp1 peptide-conjugated hybrid nanoparticles for targeting Treg cells in the tumor microenvironment. The tLyp1 peptide-modified hybrid nanoparticles presented good stability and effective targeting to Treg cells, and they enhanced the effect of imatinib in downregulating Treg cell suppression through inhibition of STAT3 and STAT5 phosphorylation...
May 16, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29776594/gearing-up-t-cell-immunotherapy-in-cervical-cancer
#3
REVIEW
Shilpa Raghuvanshi Chauhan, Mausumi Bharadwaj
The World Health Organization estimates more than 270,000 deaths annually by cervical cancer. Present vaccines are prophylactic in nature which cannot treat huge bulk of cervical cancer patients worldwide. Available therapies like radiotherapy, chemotherapy, or surgery are not effective in high-grade lesion, and hence, there is an unmet medical need for an effective form of therapy. T cells play a significant role in cervical cancer pathogenesis as human papilloma virus uses multiple mechanisms that dodge host T-cell immune-surveillance aiding in persistence of infection and establishment of cancer...
April 22, 2018: Current Problems in Cancer
https://www.readbyqxmd.com/read/29774202/loss-of-the-cyclin-dependent-kinase-inhibitor-1-in-the-context-of-brachyury-mediated-phenotypic-plasticity-drives-tumor-resistance-to-immune-attack
#4
Duane H Hamilton, Kristen K McCampbell, Claudia Palena
The acquisition of mesenchymal features by carcinoma cells is now recognized as a driver of metastasis and tumor resistance to a range of anticancer therapeutics, including chemotherapy, radiation, and certain small-molecule targeted therapies. With the recent successful implementation of immunotherapies for the treatment of various types of cancer, there is growing interest in understanding whether an immunological approach could be effective at eradicating carcinoma cells bearing mesenchymal features. Recent studies, however, demonstrated that carcinoma cells that have acquired mesenchymal features may also exhibit decreased susceptibility to lysis mediated by immune effector cells, including antigen-specific CD8+ T cells, innate natural killer (NK), and lymphokine-activated killer (LAK) cells...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29774061/immunotherapy-in-non-metastatic-non-small-cell-lung-cancer-can-the-benefits-of-stage-iv-therapy-be-translated-into-earlier-stages
#5
REVIEW
Griet Deslypere, Dorothée Gullentops, Els Wauters, Johan Vansteenkiste
Over the last decade, several steps forward in the treatment of patients with stage IV non-small cell lung cancer (NCSLC) were made. Examples are the use of pemetrexed, pemetrexed maintenance therapy, or bevacizumab for patients with nonsquamous NSCLC. A big leap forward was the use of tyrosine kinase inhibitors in patients selected on the basis of an activating oncogene, such as epidermal growth factor receptor ( EGFR ) activating mutations or anaplastic lymphoma kinase ( ALK ) translocations. However, all of these achievements could not be translated into survival benefits when studied in randomized controlled trials in patients with nonmetastatic NSCLC...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29772458/phenotyping-and-target-expression-profiling-of-cd34-cd38-and-cd34-cd38-stem-and-progenitor-cells-in-acute-lymphoblastic-leukemia
#6
Katharina Blatt, Ingeborg Menzl, Gregor Eisenwort, Sabine Cerny-Reiterer, Harald Herrmann, Susanne Herndlhofer, Gabriele Stefanzl, Irina Sadovnik, Daniela Berger, Alexandra Keller, Alexander Hauswirth, Gregor Hoermann, Michael Willmann, Thomas Rülicke, Heinz Sill, Wolfgang R Sperr, Christine Mannhalter, Junia V Melo, Ulrich Jäger, Veronika Sexl, Peter Valent
Leukemic stem cells (LSCs) are an emerging target of curative anti-leukemia therapy. In acute lymphoblastic leukemia (ALL), LSCs frequently express CD34 and often lack CD38. However, little is known about markers and targets expressed in ALL LSCs. We have examined marker- and target expression profiles in CD34+ /CD38- LSCs in patients with Ph+ ALL (n = 22) and Ph- ALL (n = 27) by multi-color flow cytometry and qPCR. ALL LSCs expressed CD19 (B4), CD44 (Pgp-1), CD123 (IL-3RA), and CD184 (CXCR4) in all patients tested...
May 14, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29772069/nature-of-tumor-rejection-antigens-in-ovarian-cancer
#7
REVIEW
Muzamil Y Want, Amit A Lugade, Sebastiano Battaglia, Kunle Odunsi
Major progress in the analysis of human immune responses to cancer has been made through the molecular characterization of human tumor antigens. The development of therapeutic strategies for eliciting immune-mediated rejection of tumors has accelerated due to the elucidation of the molecular basis for tumor cell recognition and destruction by immune cells. Of the various human tumor antigens defined to date in ovarian cancer, the cancer-testis (CT) family of antigens have studied extensively pre-clinically and clinically due their testis-restricted expression in normal tissues and ability to elicit robust immune responses...
May 17, 2018: Immunology
https://www.readbyqxmd.com/read/29771487/cancer-cell-membrane-coated-adjuvant-nanoparticles-with-mannose-modification-for-effective-anticancer-vaccination
#8
Rong Yang, Jun Xu, Ligeng Xu, Xiaoqi Sun, Qian Chen, Yuhuan Zhao, Rui Peng, Zhuang Liu
Tumor vaccines for cancer prevention and treatment have attracted tremendous interests in the area of cancer immunotherapy in recent years. In this work, we present a strategy to construct cancer vaccines by encapsulating immune-adjuvant nanoparticles with cancer cell membrane modified by mannose. Poly (D, L-lactide-co-glycolide) (PLGA) nanoparticles are firstly loaded with toll-like receptor 7 agonist, imiquimod (R837). Those adjuvant nanoparticles (NP-R) are then coated with cancer cell membranes (NP-R@M), whose surface proteins could act as tumor-specific antigens...
May 17, 2018: ACS Nano
https://www.readbyqxmd.com/read/29771386/immunotherapy-in-cns-cancers-the-role-of-immune-cell-trafficking
#9
Nivedita M Ratnam, Mark R Gilbert, Amber J Giles
Glioblastoma (GBM) is a highly malignant CNS tumor with very poor survival despite intervention with conventional therapeutic strategies. Although the CNS is separated from the immune system by the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB), emerging evidence of immune surveillance and the selective infiltration of GBMs by immune suppressive cells indicates that there is breakdown or compromise of these physical barriers. This in turn offers hope that immunotherapy can be applied to specifically target and reduce tumor burden...
May 15, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29770138/ny-eso-1-based-immunotherapy-of-cancer-current-perspectives
#10
REVIEW
Remy Thomas, Ghaneya Al-Khadairi, Jessica Roelands, Wouter Hendrickx, Said Dermime, Davide Bedognetti, Julie Decock
NY-ESO-1 or New York esophageal squamous cell carcinoma 1 is a well-known cancer-testis antigen (CTAs) with re-expression in numerous cancer types. Its ability to elicit spontaneous humoral and cellular immune responses, together with its restricted expression pattern, have rendered it a good candidate target for cancer immunotherapy. In this review, we provide background information on NY-ESO-1 expression and function in normal and cancerous tissues. Furthermore, NY-ESO-1-specific immune responses have been observed in various cancer types; however, their utility as biomarkers are not well determined...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29769722/bystander-cd8-t-cells-are-abundant-and-phenotypically-distinct-in-human-tumour-infiltrates
#11
Yannick Simoni, Etienne Becht, Michael Fehlings, Chiew Yee Loh, Si-Lin Koo, Karen Wei Weng Teng, Joe Poh Sheng Yeong, Rahul Nahar, Tong Zhang, Hassen Kared, Kaibo Duan, Nicholas Ang, Michael Poidinger, Yin Yeng Lee, Anis Larbi, Alexis J Khng, Emile Tan, Cherylin Fu, Ronnie Mathew, Melissa Teo, Wan Teck Lim, Chee Keong Toh, Boon-Hean Ong, Tina Koh, Axel M Hillmer, Angela Takano, Tony Kiat Hon Lim, Eng Huat Tan, Weiwei Zhai, Daniel S W Tan, Iain Beehuat Tan, Evan W Newell
Various forms of immunotherapy, such as checkpoint blockade immunotherapy, are proving to be effective at restoring T cell-mediated immune responses that can lead to marked and sustained clinical responses, but only in some patients and cancer types1-4 . Patients and tumours may respond unpredictably to immunotherapy partly owing to heterogeneity of the immune composition and phenotypic profiles of tumour-infiltrating lymphocytes (TILs) within individual tumours and between patients5,6 . Although there is evidence that tumour-mutation-derived neoantigen-specific T cells play a role in tumour control2,4,7-10 , in most cases the antigen specificities of phenotypically diverse tumour-infiltrating T cells are largely unknown...
May 16, 2018: Nature
https://www.readbyqxmd.com/read/29769344/efficient-delivery-of-hcmv-t-cell-antigens-by-attenuated-sendai-virus-vectors
#12
Richard Kiener, Markus Fleischmann, Marian Alexander Wiegand, Niels A W Lemmermann, Christiane Schwegler, Christine Kaufmann, Angelique Renzaho, Simone Thomas, Eva Felder, Hans Helmut Niller, Benedikt Asbach, Ralf Wagner
Human Cytomegalovirus (HCMV) represents a major cause of clinical complications during pregnancy as well as immunosuppression and the licensing of a protective HCMV vaccine remains an unmet global need. Herein, we designed and validated novel Sendai virus (SeV) vectors delivering T cell immunogens IE-1 and pp65. To enhance vector safety, we used a replication-deficient strain (rdSeV) that infects target cells in a non-productive manner while retaining viral gene expression. In this study, we explored the impact that transduction with rdSeV has on human dendritic cells (DCs) by comparing it to the parental, replication-competent Sendai virus strain (rcSeV) as well as the poxvirus strain Modified Vaccinia Ankara (MVA)...
May 16, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29769207/mitigating-sox2-potentiated-immune-escape-of-head-and-neck-squamous-cell-carcinoma-with-a-sting-inducing-nanosatellite-vaccine
#13
Yee Sun Tan, Kanokwan Sansanaphongpricha, Yuying Xie, Christopher R Donnelly, Xiaobo Luo, Blake R Heath, Xinyi Zhao, Emily L Bellile, Hongxiang Hu, Hongwei Chen, Peter J Polverini, Qianming Chen, Simon Young, Thomas E Carey, Jacques E Nör, Robert L Ferris, Gregory Wolf, Duxin Sun, Yu L Lei
PURPOSE: The response rates of Head and Neck Squamous Cell Carcinoma (HNSCC) to checkpoint blockade are below 20%. We aim to develop a mechanism-based vaccine to prevent HNSCC immune escape. EXPERIMENTAL DESIGN: We performed RNA-Seq of sensitive and resistant HNSCC cells to discover central pathways promoting resistance to immune killing. Using biochemistry, animal models, HNSCC microarray and immune cell deconvolution, we assessed the role of SOX2 in inhibiting STING-type I interferon (IFN-I) signaling-mediated anti-tumor immunity...
May 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29768164/epigenomic-guided-mass-cytometry-profiling-reveals-disease-specific-features-of-exhausted-cd8-t-cells
#14
Bertram Bengsch, Takuya Ohtani, Omar Khan, Manu Setty, Sasikanth Manne, Shaun O'Brien, Pier Federico Gherardini, Ramin Sedaghat Herati, Alexander C Huang, Kyong-Mi Chang, Evan W Newell, Niels Bovenschen, Dana Pe'er, Steven M Albelda, E John Wherry
Exhausted CD8 T (Tex) cells are immunotherapy targets in chronic infection and cancer, but a comprehensive assessment of Tex cell diversity in human disease is lacking. Here, we developed a transcriptomic- and epigenetic-guided mass cytometry approach to define core exhaustion-specific genes and disease-induced changes in Tex cells in HIV and human cancer. Single-cell proteomic profiling identified 9 distinct Tex cell clusters using phenotypic, functional, transcription factor, and inhibitory receptor co-expression patterns...
May 15, 2018: Immunity
https://www.readbyqxmd.com/read/29766776/bk-polyomavirus-immune-response-with-stress-on-bk-specific-t-cells
#15
Hany M El Hennawy
Polyomavirus-associated nephropathy is a pertinent cause of poor renal allograft survival. Absence of defensive immunity toward BK polyomavirus may favor the occurrence of BK polyomavirus-active infection and influence the progression to polyomavirus-associated nephropathy. Humoral immune responses may offer incomplete protection. In this review, available data on both humoral and cellular immunity were examined, with a concentration on BK polyomavirus-specific T cells; in addition, their roles in BK polyomavirus cellular immune response and immunotherapy were discussed...
May 16, 2018: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/29766234/the-severe-cytokine-release-syndrome-in-phase-i-trials-of-cd19-car-t-cell-therapy-a-systematic-review
#16
REVIEW
Zhen Jin, Rufang Xiang, Kai Qing, Xiaoyang Li, Yunxiang Zhang, Lining Wang, Hongming Zhu, Yuanfei Mao, Zizhen Xu, Junmin Li
CD19 chimeric antigen receptor (CAR) T cell therapy has shown impressive results in treating acute lymphoblastic leukemia (B-ALL), chronic lymphoblastic leukemia (B-CLL), and B-cell non-Hodgkin lymphoma (B-NHL) over the past few years. Meanwhile, the cytokine release syndrome (CRS), which could be moderate or even life-threatening, has emerged as the most significant adverse effect in the clinical course of this novel targeting immunotherapy. In this systematic review, we analyzed the incidence of severe CRS in 19 clinical trials selected from studies published between 2010 and 2017...
May 15, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29764863/extracorporeal-photochemotherapy-drives-monocyte-to-dendritic-cell-maturation-to-induce-anti-cancer-immunity
#17
Alessandra Ventura, Aaron Vassall, Eve Robinson, Renata Filler, Douglas Hanlon, Katrina Meeth, Harib Ezaldein, Michael Girardi, Olga Sobolev, Marcus W Bosenberg, Richard L Edelson
Extracorporeal photochemotherapy (ECP) is a cancer immunotherapy for cutaneous T cell lymphoma (CTCL) operative in more than 350 centers worldwide. While its efficacy and favorable safety profile have driven its widespread use, elucidation of its underlying mechanism has been difficult. In this study, we identify the principal contributors to the anti-cancer immunotherapeutic effects of ECP, with the goal of enhancing potency and broadening applicability to additional malignancies. First, we scaled down the clinical ECP leukocyte-processing device to mouse size...
May 15, 2018: Cancer Research
https://www.readbyqxmd.com/read/29764444/molecular-and-clinical-characterization-of-ptpn2-expression-from-rna-seq-data-of-996-brain-gliomas
#18
Peng-Fei Wang, Hong-Qing Cai, Chuan-Bao Zhang, Yan-Michael Li, Xiang Liu, Jing-Hai Wan, Tao Jiang, Shou-Wei Li, Chang-Xiang Yan
BACKGROUND: Immune checkpoint inhibitors have been shown to promote antitumor immunity and achieve durable tumor remissions. However, certain tumors are refractory to current immunotherapy. These negative results encouraged us to uncover other therapeutic targets and strategies. PTPN2 (protein tyrosine phosphatase, non-receptor type 2) has been newly identified as an immunotherapy target. Loss of PTPN2 sensitizes the tumor to immunotherapy via IFNγ signaling. METHODS: Here, we investigated the relationship between PTPN2 mRNA levels and clinical characteristics in gliomas...
May 15, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29764164/immunoregulatory-antigens-novel-targets-for-cancer-immunotherapy
#19
Ayako Wakatsuki Pedersen, Katharina L Kopp, Mads Hald Andersen, Mai-Britt Zocca
Historically, the development of cancer vaccines has focused on the central role of tumor antigens in eliciting tumor-specific immune responses, with limited success. Recent advances with checkpoint blockade approaches have brought about a renewed appreciation of the importance of targeting immune suppression in cancer patients. Here we discuss a novel approach to cancer immunotherapy, namely to target recently described T cells that uniquely control cells with immune suppressive functions. Accumulating evidence support the existence of self-reactive T cells that are specific to antigens derived from immunoregulatory proteins ("immunoregulatory antigens"), such as indoleamine 2,3-dioxygenase (IDO) and PD-L1...
April 2018: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/29763778/mage-a-antigens-as-targets-for-cancer-immunotherapy
#20
REVIEW
Erik Schooten, Alessia Di Maggio, Paul M P van Bergen En Henegouwen, Marta M Kijanka
Targeted anti-cancer therapies aim at reducing side effects while retaining their anti-cancer efficacy. Immunotherapies e.g. monoclonal antibodies, adoptive T cell therapy and cancer vaccines are used to combat cancer, but the number of available cancer specific targets is limited and new approaches are needed to generate more effective and patient tailored treatments. Unique cancer intracellular epitopes can be presented on the cell surface by MHC class I molecules, which can function as epitopes for targeted therapies...
April 26, 2018: Cancer Treatment Reviews
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