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immunotherapy of cancer

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https://www.readbyqxmd.com/read/28723893/in-vivo-crispr-screening-identifies-ptpn2-as-a-cancer-immunotherapy-target
#1
Robert T Manguso, Hans W Pope, Margaret D Zimmer, Flavian D Brown, Kathleen B Yates, Brian C Miller, Natalie B Collins, Kevin Bi, Martin W LaFleur, Vikram R Juneja, Sarah A Weiss, Jennifer Lo, David E Fisher, Diana Miao, Eliezer Van Allen, David E Root, Arlene H Sharpe, John G Doench, W Nicholas Haining
Immunotherapy with PD-1 checkpoint blockade is effective in only a minority of patients with cancer, suggesting that additional treatment strategies are needed. Here we use a pooled in vivo genetic screening approach using CRISPR-Cas9 genome editing in transplantable tumours in mice treated with immunotherapy to discover previously undescribed immunotherapy targets. We tested 2,368 genes expressed by melanoma cells to identify those that synergize with or cause resistance to checkpoint blockade. We recovered the known immune evasion molecules PD-L1 and CD47, and confirmed that defects in interferon-γ signalling caused resistance to immunotherapy...
July 19, 2017: Nature
https://www.readbyqxmd.com/read/28723489/immunotherapy-for-renal-cancer-sequencing-and-combinations
#2
REVIEW
Grant D Stewart, Maria De Santis, Bernard Escudier, Thomas Powles, Guru Sonpavde
CONTEXT: Current therapy for renal cell carcinoma (RCC) generally consists of the sequential administration of single agent therapy. Given the advent of T-cell checkpoint inhibitors, the role of combinations including these agents is being intensely interrogated. OBJECTIVE: To evaluate ongoing trials of combinations including immunotherapy and sequencing of agents to treat RCC. EVIDENCE ACQUISITION: Recent data and ongoing trials were analyzed to evaluate the direction of research in this arena...
December 15, 2016: European Urology Focus
https://www.readbyqxmd.com/read/28723478/low-t-cell-receptor-diversity-high-somatic-mutation-burden-and-high-neoantigen-load-as-predictors-of-clinical-outcome-in-muscle-invasive-bladder-cancer
#3
Noura J Choudhury, Kazuma Kiyotani, Kai Lee Yap, Alexa Campanile, Tatjana Antic, Poh Yin Yew, Gary Steinberg, Jae Hyun Park, Yusuke Nakamura, Peter H O'Donnell
BACKGROUND: The success of cancer immunotherapies has highlighted the potent ability of local adaptive immune responses to eradicate cancer cells by targeting neoantigens generated by somatic alterations. However, how these factors interact to drive the natural history of muscle-invasive bladder cancer (MIBC) is not well understood. OBJECTIVE: To investigate the role of immune regulation in MIBC disease progression, we performed massively parallel T-cell receptor (TCR) sequencing of tumor-infiltrating T cells (TILs), in silico neoantigen prediction from exome sequences, and expression analysis of immune-related genes...
October 2016: European Urology Focus
https://www.readbyqxmd.com/read/28722451/-basal-cell-carcinoma-and-the-modalities-of-its-therapy
#4
Petr Arenberger, Jiří Ettler
Basal cell carcinoma (BCC) also known as basalioma or basal cell cancer, is the most common skin cancer. BCC has a very low metastatic risk. This tumor can cause significant disfigurement by invading surrounding tissues. It occurs mainly in fair-skinned patients with a family history of this cancer. Sunlight is a factor in about two-thirds of these cancers. Standard surgical excision is the treatment of choice. Mohs micrographic surgery is an outpatient or inpatient procedure in which the tumor is surgically excised and then immediately examined under a microscope...
2017: Casopís Lékar̆ů C̆eských
https://www.readbyqxmd.com/read/28721449/role-of-regulatory-t-cells-in-acute-myeloid-leukemia-patients-undergoing-relapse-preventive-immunotherapy
#5
Frida Ewald Sander, Malin Nilsson, Anna Rydström, Johan Aurelius, Rebecca E Riise, Charlotta Movitz, Elin Bernson, Roberta Kiffin, Anders Ståhlberg, Mats Brune, Robin Foà, Kristoffer Hellstrand, Fredrik B Thorén, Anna Martner
Regulatory T cells (Tregs) have been proposed to dampen functions of anti-neoplastic immune cells and thus promote cancer progression. In a phase IV trial (Re:Mission Trial, NCT01347996, http://www.clinicaltrials.gov ) 84 patients (age 18-79) with acute myeloid leukemia (AML) in first complete remission (CR) received ten consecutive 3-week cycles of immunotherapy with histamine dihydrochloride (HDC) and low-dose interleukin-2 (IL-2) to prevent relapse of leukemia in the post-consolidation phase. This study aimed at defining the features, function and dynamics of Foxp3(+)CD25(high)CD4(+) Tregs during immunotherapy and to determine the potential impact of Tregs on relapse risk and survival...
July 18, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28720686/oncolytic-virus-induced-cell-death-and-immunity-a-match-made-in-heaven
#6
REVIEW
Jolien De Munck, Alex Binks, Iain A McNeish, Joeri L Aerts
Our understanding of the mechanisms responsible for cancer development has increased enormously over the last decades. However, for many cancers, this has not been translated into a significant improvement in overall survival, and overall mortality remains high. Treatment for many malignancies remains based on surgery, chemotherapy, and radiotherapy. Significant progress has been made toward the development of more specific, more potent, and less invasive treatment modalities, but such targeted therapies remain the exception for most cancers...
July 18, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28719055/endocrine-toxicity-of-immune-checkpoint-inhibitors-essential-crosstalk-between-endocrinologists-and-oncologists
#7
REVIEW
Frédéric Illouz, Claire Briet, Lucie Cloix, Yannick Le Corre, Nathalie Baize, Thierry Urban, Ludovic Martin, Patrice Rodien
Two types of immune checkpoint inhibitors, both antibodies that target cytotoxic T-lymphocyte antigen-4 and those that target programmed cell death-protein 1, have been approved for use in melanoma, non-small-cell lung cancer, and renal cell carcinoma as first-line or second-line therapy. Their adverse events are primarily regarded as immune-related adverse events. We felt it was important to pinpoint and discuss certain preconceptions or misconceptions regarding thyroid dysfunction, hypophysitis, and diabetes induced by immune checkpoint inhibitors...
July 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28718815/regional-delivery-of-chimeric-antigen-receptor-car-t-cells-for-cancer-therapy
#8
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/28718409/metronomic-chemotherapy-direct-targeting-of-cancer-cells-after-all
#9
REVIEW
Nicolas André, Kelvin Tsai, Manon Carré, Eddy Pasquier
Metronomic chemotherapy (MC) was initially described as an antiangiogenic therapy more than 15 years ago. Over the past few years, additional data have highlighted the impact of MC on the microenvironment beyond angiogenesis, with, most importantly, a potential impact on the immune system. Here, we review and reappraise the fact that MC might be able to directly kill cancer cells. Although long neglected, this question is of critical importance both fundamentally and clinically, especially when considering future associations with immunotherapies...
May 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28718331/entinostat-for-the-treatment-of-breast-cancer
#10
Dario Trapani, Angela Esposito, Carmen Criscitiello, Luca Mazzarella, Marzia Locatelli, Ida Minchella, Saverio Minucci, Giuseppe Curigliano
Breast cancer accounts for 29% of malignant tumors. It is an heterogenous disease covering a spectrum of different molecular subtypes. Epigenetic aberrations may affect gene expression through DNA and histone proteins modifications thus promoting tumor progression and resistance to anti- tumor treatment. Area covered: This article explores the potential role of entinostat in the treatment of breast cancer. The clinical trials evaluating entinostat are discussed, highlighting preclinical data and early-phase clinical studies results...
July 18, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28716945/evaluating-optimal-therapy-robustness-by-virtual-expansion-of-a-sample-population-with-a-case-study-in-cancer-immunotherapy
#11
Syndi Barish, Michael F Ochs, Eduardo D Sontag, Jana L Gevertz
Cancer is a highly heterogeneous disease, exhibiting spatial and temporal variations that pose challenges for designing robust therapies. Here, we propose the VEPART (Virtual Expansion of Populations for Analyzing Robustness of Therapies) technique as a platform that integrates experimental data, mathematical modeling, and statistical analyses for identifying robust optimal treatment protocols. VEPART begins with time course experimental data for a sample population, and a mathematical model fit to aggregate data from that sample population...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28716899/hdac1-upregulation-by-nanog-promotes-multidrug-resistance-and-a-stem-like-phenotype-in-immune-edited-tumor-cells
#12
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
#13
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/28716463/combination-strategies-on-the-basis-of-immune-checkpoint-inhibitors-in-non-small-cell-lung-cancer-where-do-we-stand
#14
REVIEW
Meng Qiao, Tao Jiang, Shengxiang Ren, Caicun Zhou
The era of immune checkpoint inhibitors, especially programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) antibodies in the treatment of advanced non-small-cell lung cancer (NSCLC) is coming. Because of the lack of the definite biomarkers to select the optimal responders, only approximately 20% of patients with advanced NSCLC would respond to single checkpoint inhibitors-based immunotherapy. Moreover, primary or acquired resistance to conventional therapies is inevitable in most cases. Thus, combinations are pushed to move forward to be an alternative strategy and surely, it would be a future direction...
June 23, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28716121/identification-of-trunk-mutations-in-gastric-carcinoma-a-case-study
#15
Zhan Zhou, Shanshan Wu, Jun Lai, Yuan Shi, Chixiao Qiu, Zhe Chen, Yufeng Wang, Xun Gu, Jie Zhou, Shuqing Chen
BACKGROUND: Intratumor heterogeneity (ITH) poses an urgent challenge for cancer precision medicine because it can cause drug resistance against cancer target therapy and immunotherapy. The search for trunk mutations that are present in all cancer cells is therefore critical for each patient. CASE PRESENTATION: In this study, we aimed to evaluate the efficiency of multiregional sequencing for the identification of trunk mutations present in all regions of a tumor as a case study...
July 17, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28716106/acute-interstitial-nephritis-after-sequential-ipilumumab-nivolumab-therapy-of-metastatic-melanoma
#16
Lea Bottlaender, Anne-Laure Breton, Louis de Laforcade, Frederique Dijoud, Luc Thomas, Stephane Dalle
BACKGROUND: The anti-Programmed Death receptor 1 (anti-PD-1) antibodies nivolumab and pembrolizumab are new treatments in metastatic melanoma. Immunotherapies are best known to be responsible for thrombotic microangiopathy. However, immune interstitial nephritis has been described in a patient treated by nivolumab and ipilimumab concomitantly, and three cases of granulomatous interstitial nephritis have been reported with ipilimumab monotherapy. We report herein a case of acute interstitial immune nephritis in a patient treated with nivolumab after ipilimumab for pulmonary metastatic melanoma...
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
#17
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/28716069/angiosarcoma-treated-successfully-with-anti-pd-1-therapy-a-case-report
#18
Simran Sindhu, Lana H Gimber, Lee Cranmer, Ali McBride, Andrew S Kraft
BACKGROUND: Angiosarcomas are tumors of malignant endothelial origin that have a poor prognosis with a five-year survival of less than 40%. These tumors can be found in all age groups, but are more common in older patients; with the cutaneous form most common in older white men. Combined modality therapy including surgery and radiation appears to have a better outcome than each modality alone. When metastatic, agents such as liposomal doxorubicin, paclitaxel and ifosfamide have activity but it is short-lived and not curative...
July 18, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28716068/highlights-of-the-31st-annual-meeting-of-the-society-for-immunotherapy-of-cancer-sitc-2016
#19
REVIEW
James L Gulley, Elizabeth A Repasky, Laura S Wood, Lisa H Butterfield
Therapeutic efforts to engage the immune system against cancer have yielded exciting breakthroughs and a growing list of approved immune-based agents across a variety of disease states. Despite the early successes and durable responses associated with treatments such as immune checkpoint inhibition, there is still progress to be made in the field of cancer immunotherapy. The 31st annual meeting of the Society for Immunotherapy of Cancer (SITC 2016), which took place November 11-13, 2016 in National Harbor, Maryland, showcased the latest advancements in basic, translational, and clinical research focused on cancer immunology and immunotherapy...
July 18, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28716061/colony-stimulating-factor-1-receptor-csf1r-inhibitors-in-cancer-therapy
#20
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
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