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Immunogenic cell death

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https://www.readbyqxmd.com/read/29147614/exploiting-a-new-strategy-to-induce-immunogenic-cell-death-to-improve-dendritic-cell-based-vaccines-for-lymphoma-immunotherapy
#1
B Montico, C Lapenta, M Ravo, D Martorelli, E Muraro, B Zeng, E Comaro, M Spada, S Donati, S M Santini, R Tarallo, G Giurato, F Rizzo, A Weisz, F Belardelli, R Dolcetti, J Dal Col
Although promising, the clinical benefit provided by dendritic cell (DC)-based vaccines is still limited and the choice of the optimal antigen formulation is still an unresolved issue. We have developed a new DC-based vaccination protocol for aggressive and/or refractory lymphomas which combines the unique features of interferon-conditioned DC (IFN-DC) with highly immunogenic tumor cell lysates (TCL) obtained from lymphoma cells undergoing immunogenic cell death. We show that treatment of mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) cell lines with 9-cis-retinoic acid and IFNα (RA/IFNα) induces early membrane exposure of Calreticulin, HSP70 and 90 together with CD47 down-regulation and enhanced HMGB1 secretion...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147611/chloroquine-supplementation-increases-the-cytotoxic-effect-of-curcumin-against-her2-neu-overexpressing-breast-cancer-cells-in-vitro-and-in-vivo-in-nude-mice-while-counteracts-it-in-immune-competent-mice
#2
L Masuelli, M Granato, M Benvenuto, R Mattera, R Bernardini, M Mattei, G d'Amati, G D'Orazi, A Faggioni, R Bei, M Cirone
Autophagy is usually a pro-survival mechanism in cancer cells, especially in the course of chemotherapy, thus autophagy inhibition may enhance the chemotherapy-mediated anti-cancer effect. However, since autophagy is strongly involved in the immunogenicity of cell death by promoting ATP release, its inhibition may reduce the immune response against tumors, negatively influencing the overall outcome of chemotherapy. In this study, we evaluated the in vitro and in vivo anti-cancer effect of curcumin (CUR) against Her2/neu overexpressing breast cancer cells (TUBO) in the presence or in the absence of the autophagy inhibitor chloroquine (CQ)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147605/egfr-mutation-correlates-with-uninflamed-phenotype-and-weak-immunogenicity-causing-impaired-response-to-pd-1-blockade-in-non-small-cell-lung-cancer
#3
Zhong-Yi Dong, Jia-Tao Zhang, Si-Yang Liu, Jian Su, Chao Zhang, Zhi Xie, Qing Zhou, Hai-Yan Tu, Chong-Rui Xu, Li-Xu Yan, Yu-Fa Li, Wen-Zhao Zhong, Yi-Long Wu
Patients with EGFR mutations showed unfavorable response to programmed cell death-1 (PD-1) blockade immunotherapy in non-small cell lung cancer (NSCLC). Yet the underlying association between EGFR mutation and immune resistance remains largely unclear. We performed an integrated analysis of PD-ligand 1(PD-L1)/CD8 expression and mutation profile based on the repository database and resected early-stage NSCLC in Guangdong Lung Cancer Institute (GLCI). Meanwhile, 2 pool-analyses were set to clarify the correlation between EGFR mutation and PD-L1 expression, and the association of EGFR status with response to anti-PD-1/L1 therapy...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29146246/nanoparticle-formulation-improves-doxorubicin-efficacy-by-enhancing-host-antitumor-immunity
#4
Eric M Mastria, Leon Y Cai, Matthew J Kan, Xinghai Li, Jeffrey L Schaal, Steven Fiering, Michael D Gunn, Mark W Dewhirst, Smita K Nair, Ashutosh Chilkoti
Strategies that enhance the host antitumor immune response promise to revolutionize cancer therapy. Optimally mobilizing the immune system will likely require a multi-pronged approach to overcome the resistance developed by tumors to therapy. Recently, it has become recognized that doxorubicin can contribute to re-establishing host antitumor immunity through the generation of immunogenic cell death. However, the potential for delivery strategies to further enhance the immunological effects of doxorubicin has not been adequately examined...
November 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29144754/immunogenic-cell-death-amplified-by-co-localized-adjuvant-delivery-for-cancer-immunotherapy
#5
Yuchen Fan, Rui Kuai, Yao Xu, Lukasz J Ochyl, Darrell J Irvine, James Moon
Despite their potential, conventional whole-cell cancer vaccines prepared by freeze-thawing or irradiation have shown limited therapeutic efficacy in clinical trials. Recent studies have shown that cancer cells treated with certain chemotherapeutics, such as mitoxantrone, can undergo immunogenic cell death (ICD) and initiate anti-tumor immune responses. However, it remains unclear how ICD can be exploited for cancer immunotherapy. Here, we present a new biomaterial-based strategy for converting immunogenically dying tumor cells into a powerful platform for cancer vaccination and demonstrate their immunogenicity in murine models of melanoma and colon carcinoma...
November 16, 2017: Nano Letters
https://www.readbyqxmd.com/read/29143550/safety-and-tolerability-of-inebilizumab-medi-551-an-anti-cd19-monoclonal-antibody-in-patients-with-relapsing-forms-of-multiple-sclerosis-results-from-a-phase-1-randomised-placebo-controlled-escalating-intravenous-and-subcutaneous-dose-study
#6
Mark A Agius, Gabriela Klodowska-Duda, Maciej Maciejowski, Andrzej Potemkowski, Jing Li, Kaushik Patra, Jacob Wesley, Soraya Madani, Gerard Barron, Eliezer Katz, Armando Flor
BACKGROUND: B cells may be involved in the pathophysiology of multiple sclerosis (MS). Inebilizumab (formerly MEDI-551) binds to and depletes CD19(+) B cells. OBJECTIVES: To assess safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of inebilizumab in adults with relapsing MS. METHODS: This phase 1 trial randomised 28 patients 3:1 (21, inebilizumab; 7, placebo) to inebilizumab (2 intravenous (IV) doses, days 1 and 15: 30, 100 or 600 mg; or single subcutaneous (SC) dose on day 1: 60 or 300 mg) or matching placebo, with follow-up until at least week 24 or return of CD19(+) B-cell count to ⩾80 cells/µL...
November 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29143114/cancer-vaccine-strategies-translation-from-mice-to-human-clinical-trials
#7
REVIEW
Jay A Berzofsky, Masaki Terabe, Jane B Trepel, Ira Pastan, David F Stroncek, John C Morris, Lauren V Wood
We translated two cancer vaccine strategies from mice into human clinical trials. (1) In preclinical studies on TARP, an antigen expressed in most prostate cancers, we mapped epitopes presented by HLA-A*0201, modified them to increase affinity and immunogenicity in HLA transgenic mice, and induced human T cells that killed human cancer cells ("epitope enhancement"). In a clinical trial, HLA-A2(+) prostate cancer patients with PSA biochemical recurrence (Stage D0) were vaccinated with two peptides either in Montanide-ISA51 or on autologous dendritic cells (DCs)...
November 15, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29142131/single-dose-trivalent-vesiculovax-vaccine-protects-macaques-from-lethal-ebolavirus-and-marburgvirus-challenge
#8
Demetrius Matassov, Chad E Mire, Theresa Latham, Joan B Geisbert, Rong Xu, Ayuko Ota-Setlik, Krystle N Agans, Dean J Kobs, Morgan Q S Wendling, Amanda Burnaugh, Thomas L Rudge, Carol L Sabourin, Michael A Egan, David K Clarke, Thomas W Geisbert, John H Eldridge
Previous studies demonstrated that a single intramuscular (IM) dose of an attenuated vesicular stomatitis virus vector (Vesiculovax™, rVSV-N4CT1) expressing the glycoprotein (GP) from the Mayinga strain of Zaire ebolavirus (EBOV) protected nonhuman primates (NHP) from lethal challenge with EBOV Kikwit and Makona strains. Here we studied the immunogenicity of an expanded range of attenuated rVSV vectors expressing filovirus GP in mice. Based on data from those studies an optimal attenuated tri-valent rVSV vector formulation was identified which included rVSV vectors expressing EBOV, Sudan ebolavirus (SUDV) or Angola strain of Marburg marburgvirus (MARV) GPs...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29138861/immunogenic-tumor-cell-death-induced-by-chemotherapy-in-patients-with-breast-cancer-and-esophageal-squamous-cell-carcinoma
#9
Keita Aoto, Kousaku Mimura, Hirokazu Okayama, Motonobu Saito, Shun Chida, Masaru Noda, Takahiro Nakajima, Katsuharu Saito, Noriko Abe, Shinji Ohki, Tohru Ohtake, Seiichi Takenoshita, Koji Kono
It has been reported that chemo-radiotherapy can induce immunogenic tumor cell death (ICD), which triggers T-cell immunity mainly mediated by high-mobility group box 1 protein (HMGB1) and calreticulin. However, there is still limited information to support this theory relating to chemotherapy alone. In the present study, the expression of HMGB1 and calreticulin was evaluated by immunohistochemistry in pre-treatment biopsy specimens and surgically resected specimens, which were obtained from patients with breast cancer (n=52) and esophageal squamous cell carcinoma (ESCC) (n=8) who had been treated with neoadjuvant chemotherapy (NAC)...
November 14, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29135265/evaluation-of-early-therapeutic-effects-after-near-infrared-photoimmunotherapy-nir-pit-using-luciferase-luciferin-photon-counting-and-fluorescence-imaging
#10
Yasuhiro Maruoka, Tadanobu Nagaya, Yuko Nakamura, Kazuhide Sato, Fusa Ogata, Shuhei Okuyama, Peter L Choyke, Hisataka Kobayashi
Near infrared photoimmunotherapy (NIR-PIT) is a newly-developed cancer treatment that induces highly selective immunogenic cell death. It is based on an antibody-photo-absorber conjugate (APC) that is activated by NIR light. The purpose of this study was to investigate the effects of NIR-PIT as measured by luciferase-luciferin photon-counting and fluorescence imaging. Six days after subcutaneous injection of A431-luc-GFP cells tumors formed in a xenograft mouse model. The EGFR-targeting antibody, panitumumab was conjugated to the photoabsorber, IRDye-700DX (pan-IR700) and was intravenously administered to tumor-bearing mice...
November 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29134676/a-safety-and-immunogenicity-study-of-a-novel-subunit-plague-vaccine-in-cynomolgus-macaques
#11
Li Liu, Dong Wei, Zhe Qu, Li Sun, Yufa Miao, Yanwei Yang, Jinbiao Lu, Weixin Du, Bingxiang Wang, Bo Li
Plague has led to millions of deaths in history and outbreaks continue to the present day. The efficacy limitations and safety concerns of the existing killed whole cell and live-attenuated vaccines call for the development of new vaccines. In this study, we evaluated the immunogenicity and safety of a novel subunit plague vaccine, comprising native F1 antigen and recombinant V antigen. The cynomolgus macaques in low- and high-dose vaccine groups were vaccinated at weeks 0, 2, 4 and 6, at dose levels of 15 μg F1 + 15 μg rV and 30 μg F1 + 30 μg rV respectively...
November 14, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29126088/in-the-immuno-oncology-era-is-anti-pd-1-or-anti-pd-l1-immunotherapy-modifying-the-sensitivity-to-conventional-cancer-therapies
#12
Sandrine Aspeslagh, Margarida Matias, Virginia Palomar, Laurent Dercle, Emilie Lanoy, Jean-Charles Soria, Sophie Postel-Vinay
INTRODUCTION: The advent of anti-programmed death receptor-1/ligand-1 antibodies (anti-PD(L)1) is profoundly changing the therapeutic strategy of oncology. As anti-PD(L)1 modulate tumour microenvironment, it might impact sensitivity to conventional cancer therapy (CCT). Therefore, we explored whether sensitivity to CCT was different before and after anti-PD(L)1 therapy. METHODS: Patients who started anti-PD(L)1 treatment at Gustave Roussy Cancer Centre between February 2012 and December 2015, and who received at least one line of CCT immediately before and immediately after anti-PD(L)1, were eligible...
November 7, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29123967/ionizing-radiation-sensitizes-tumors-to-pd-l1-immune-checkpoint-blockade-in-orthotopic-murine-head-and-neck-squamous-cell-carcinoma
#13
Ayman Oweida, Shelby Lennon, Dylan Calame, Sean Korpela, Shilpa Bhatia, Jaspreet Sharma, Caleb Graham, David Binder, Natalie Serkova, David Raben, Lynn Heasley, Eric Clambey, Raphael Nemenoff, Sana D Karam
Immunotherapy clinical trials targeting the programmed-death ligand axis (PD-1/PD-L1) show that most head and neck squamous cell carcinoma (HNSCC) patients are resistant to PD-1/PD-L1 inhibition. We investigated whether local radiation to the tumor can transform the immune landscape and render poorly immunogenic HNSCC tumors sensitive to PD-L1 inhibition. We used the first novel orthotopic model of HNSCC with genetically distinct murine cell lines. Tumors were resistant to PD-L1 checkpoint blockade, harbored minimal PD-L1 expression and tumor infiltrating lymphocytes at baseline, and were resistant to radiotherapy...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29123948/no-patient-left-behind-the-promise-of-immune-priming-with-epigenetic-agents
#14
REVIEW
Corey A Carter, Bryan T Oronsky, Joseph Roswarski, Arnold L Oronsky, Neil Oronsky, Jan Scicinski, Harry Lybeck, Michelle M Kim, Michelle Lybeck, Tony R Reid
Checkpoint inhibitors, monoclonal antibodies that inhibit PD-1 or CTLA-4, have revolutionized the treatment of multiple cancers. Despite the enthusiasm for the clinical successes of checkpoint inhibitors, and immunotherapy, in general, only a minority of patients with specific tumor types actually benefit from treatment. Emerging evidence implicates epigenetic alterations as a mechanism of clinical resistance to immunotherapy. This review presents evidence for that association, summarizes the epi-based mechanisms by which tumors evade immunogenic cell death, discusses epigenetic modulation as a component of an integrated strategy to boost anticancer T cell effector function in relation to a tumor immunosuppression cycle and, finally, makes the case that the success of this no-patient-left-behind strategy critically depends on the toxicity profile of the epigenetic agent(s)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29123364/corneal-lenticule-storage-before-reimplantation
#15
Yu-Chi Liu, Geraint P Williams, Ben L George, Yu Qiang Soh, Xin Yi Seah, Gary Swee Lim Peh, Gary Hin Fai Yam, Jodhbir S Mehta
Purpose: To explore the optimal lenticule storage conditions that maintain lenticule integrity and clarity. Methods: A total of 99 lenticules obtained from myopic patients undergoing small incision lenticule extraction (SMILE) were divided into four combinations for short-term storage conditions: PBS, Dulbecco's Modified Eagle's Medium (DMEM), Optisol GS, or anhydrous glycerol. Two thirds of the lenticules were further stored for 4 weeks under eight different conditions...
2017: Molecular Vision
https://www.readbyqxmd.com/read/29123260/combining-dna-damaging-therapeutics-with-immunotherapy-more-haste-less-speed
#16
REVIEW
Jessica S Brown, Raghav Sundar, Juanita Lopez
The idea that chemotherapy can be used in combination with immunotherapy may seem somewhat counterproductive, as it can theoretically eliminate the immune cells needed for antitumour immunity. However, much preclinical work has now demonstrated that in addition to direct cytotoxic effects on cancer cells, a proportion of DNA damaging agents may actually promote immunogenic cell death, alter the inflammatory milieu of the tumour microenvironment and/or stimulate neoantigen production, thereby activating an antitumour immune response...
November 9, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29118755/apoptotic-cells-induced-signaling-for-immune-homeostasis-in-macrophages-and-dendritic-cells
#17
REVIEW
Uriel Trahtemberg, Dror Mevorach
Inefficient and abnormal clearance of apoptotic cells (efferocytosis) contributes to systemic autoimmune disease in humans and mice, and inefficient chromosomal DNA degradation by DNAse II leads to systemic polyarthritis and a cytokine storm. By contrast, efficient clearance allows immune homeostasis, generally leads to a non-inflammatory state for both macrophages and dendritic cells (DCs), and contributes to maintenance of peripheral tolerance. As many as 3 × 10(8) cells undergo apoptosis every hour in our bodies, and one of the primary "eat me" signals expressed by apoptotic cells is phosphatidylserine (PtdSer)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29108228/cbp501-induces-immunogenic-tumor-cell-death-and-cd8-t-cell-infiltration-into-tumors-in-combination-with-platinum-and-increases-the-efficacy-of-immune-checkpoint-inhibitors-against-tumors-in-mice
#18
Keiichi Sakakibara, Takuji Sato, Donald W Kufe, Daniel D VonHoff, Takumi Kawabe
CBP501, a calmodulin-binding peptide, is an anti-cancer drug candidate and functions as an enhancer of platinum uptake into cancer cells. Here we show that CBP501 promotes immunogenic cell death (ICD) in combination with platinum agents. CBP501 enhanced a clinically relevant low dose of cisplatin (CDDP) in vitro as evidenced by upregulation of ICD markers, including cell surface calreticulin exposure and release of high-mobility group protein box-1. Synergistic induction of ICD by CDDP plus CBP501 as compared to CDDP alone was confirmed in the well-established vaccination assay...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29103968/anti-pd-l1-tgf%C3%AE-r2-m7824-fusion-protein-induces-immunogenic-modulation-of-human-urothelial-carcinoma-cell-lines-rendering-them-more-susceptible-to-immune-mediated-recognition-and-lysis
#19
Italia Grenga, Renee N Donahue, Morgan L Gargulak, Lauren M Lepone, Mario Roselli, Marijo Bilusic, Jeffrey Schlom
BACKGROUND: Avelumab has recently been approved by the Food and Drug Administration for the therapy of Merkel cell carcinoma and urothelial carcinoma. M7824 is a novel first-in-class bifunctional fusion protein comprising a monoclonal antibody against programmed death-ligand 1 (PD-L1, avelumab), fused to the extracellular domain of human transforming growth factor beta (TGFβ) receptor 2, which functions as a TGFβ "trap." Advanced urothelial tumors have been shown to express TGFβ, which possesses immunosuppressive properties that promote cancer progression and metastasis...
November 2, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/29100312/molecular-signatures-reflecting-microenvironmental-metabolism-and-chemotherapy-induced-immunogenic-cell-death-in-colorectal-liver-metastases
#20
Olga Østrup, Vegar Johansen Dagenborg, Einar Andreas Rødland, Veronica Skarpeteig, Laxmi Silwal-Pandit, Krzysztof Grzyb, Audun Elnæs Berstad, Åsmund Avdem Fretland, Gunhild Mari Mælandsmo, Anne-Lise Børresen-Dale, Anne Hansen Ree, Bjørn Edwin, Vigdis Nygaard, Kjersti Flatmark
Background: Metastatic colorectal cancer (CRC) is associated with highly variable clinical outcome and response to therapy. The recently identified consensus molecular subtypes (CMS1-4) have prognostic and therapeutic implications in primary CRC, but whether these subtypes are valid for metastatic disease is unclear. We performed multi-level analyses of resectable CRC liver metastases (CLM) to identify molecular characteristics of metastatic disease and evaluate the clinical relevance...
September 29, 2017: Oncotarget
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