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Immunotherapy for lung cancer

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https://www.readbyqxmd.com/read/28088513/an-immunogram-for-the-cancer-immunity-cycle-towards-personalized-immunotherapy-of-lung-cancer
#1
Takahiro Karasaki, Kazuhiro Nagayama, Hideki Kuwano, Jun-Ichi Nitadori, Masaaki Sato, Masaki Anraku, Akihiro Hosoi, Hirokazu Matsushita, Yasuyuki Morishita, Kosuke Kashiwabara, Masaki Takazawa, Osamu Ohara, Kazuhiro Kakimi, Jun Nakajima
INTRODUCTION: The interaction of immune cells and cancer cells shapes the immunosuppressive tumor microenvironment. For successful cancer immunotherapy, comprehensive knowledge of anti-tumor immunity as a dynamic spacio-temporal process is required for each individual patient. To this end, we developed an immunogram for the cancer-immunity cycle using next-generation sequencing. METHODS: Whole-exome sequencing and RNA-Seq was performed in 20 non-small cell lung cancer patients (12 adenocarcinoma, 7 squamous cell carcinoma, and 1 large cell neuroendocrine carcinoma)...
January 11, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28074864/a-novel-monoclonal-antibody-targeting-coxsackie-virus-and-adenovirus-receptor-inhibits-tumor-growth-in-vivo
#2
Manabu Kawada, Hiroyuki Inoue, Masunori Kajikawa, Masahito Sugiura, Shuichi Sakamoto, Sakiko Urano, Chigusa Karasawa, Ihomi Usami, Mitsuru Futakuchi, Tohru Masuda
To create a new anti-tumor antibody, we conducted signal sequence trap by retrovirus-meditated expression method and identified coxsackie virus and adenovirus receptor (CXADR) as an appropriate target. We developed monoclonal antibodies against human CXADR and found that one antibody (6G10A) significantly inhibited the growth of subcutaneous as well as orthotopic xenografts of human prostate cancer cells in vivo. Furthermore, 6G10A also inhibited other cancer xenografts expressing CXADR, such as pancreatic and colorectal cancer cells...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28073845/agreement-between-programmed-cell-death-ligand-1-diagnostic-assays-across-multiple-protein-expression-cut-offs-in-non-small-cell-lung-cancer
#3
Marianne J Ratcliffe, Alan Sharpe, Anita Midha, Craig Barker, Marietta Scott, Paul Scorer, Hytham Al-Masri, Marlon Rebelatto, Jill Walker
PURPOSE: agents:Immunotherapies targeting programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) demonstrate encouraging antitumor activity and manageable tolerability in non-small cell lung cancer (NSCLC), especially in patients with high tumor PD-L1 expression, as detected by companion or complementary diagnostic assays developed for individual agents. A laboratory is unlikely to use multiple assay platforms. Furthermore, commercially available diagnostic assays are not standardized and different assay methods could lead to inappropriate treatment selection...
January 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28067949/fda-approves-breakthrough-immunotherapy-for-patients-with-non-small-cell-lung-cancer
#4
Carrie Printz
No abstract text is available yet for this article.
January 1, 2017: Cancer
https://www.readbyqxmd.com/read/28064556/pd-1-checkpoint-blockade-alone-or-combined-pd-1-and-ctla-4-blockade-as-immunotherapy-for-lung-cancer
#5
Tawee Tanvetyanon, Jhanelle E Gray, Scott J Antonia
Signaling through T-cell surface, an immune checkpoint protein such as PD-1 or CTLA-4 helps dampen or terminate unwanted immune responses. Blocking a single immune checkpoint or multiple checkpoints simultaneously can generate anti-tumor activity against a variety of cancers including lung cancer. Area covered: This review highlights the results of recent clinical studies of single or combination checkpoint inhibitor immunotherapy in non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC). The authors discuss pembrolizumab and pembrolizumab plus ipilimumab, durvalumab and durvalumab plus tremelimumab, nivolumab and nivolumab plus ipilimumab for NSCLC as well as nivolumab and nivolumab plus ipilimumab for SCLC...
January 9, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28063623/immune-checkpoint-inhibitors-in-lung-cancer-an-unheralded-opportunity
#6
R Marshall, A Popple, T Kordbacheh, J Honeychurch, C Faivre-Finn, T Illidge
Lung cancer remains the leading cause of cancer-related death worldwide, with non-small cell lung cancer accounting for 85% of the disease. Over 70% of patients present with locally advanced, non-resectable or metastatic disease and despite improvements in chemoradiotherapy regimens and the development of molecularly targeted agents, 5 year survival rates remain poor, with acquired resistance to novel targeted therapies becoming a growing concern. Currently there remains an unmet need in effectively treating and inducing durable responses in advanced disease...
January 4, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/28062694/effective-combination-of-innate-and-adaptive-immunotherapeutic-approaches-in-a-mouse-melanoma-model
#7
Alexander L Rakhmilevich, Mildred Felder, Lauren Lever, Jacob Slowinski, Kayla Rasmussen, Anna Hoefges, Tyler J Van De Voort, Hans Loibner, Alan J Korman, Stephen D Gillies, Paul M Sondel
Most cancer immunotherapies include activation of either innate or adaptive immune responses. We hypothesized that the combined activation of both innate and adaptive immunity will result in better antitumor efficacy. We have previously shown the synergy of an agonistic anti-CD40 mAb (anti-CD40) and CpG-oligodeoxynucleotides in activating macrophages to induce tumor cell killing in mice. Separately, we have shown that a direct intratumoral injection of immunocytokine (IC), an anti-GD2 Ab linked to IL-2, can activate T and NK cells resulting in antitumor effects...
January 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28059852/immune-checkpoint-inhibitors-in-first-line-therapy-of-advanced-non-small-cell-lung-cancer
#8
Jordi Remon, Benjamin Besse
PURPOSE OF REVIEW: Evading immune destruction is a hallmark of cancer. The first therapeutic wave in immunotherapies comprised a series of monoclonal antibodies directed against the immune checkpoint molecules cytotoxic T-lymphocyte-associated protein 4, programmed death 1 (PD-1), and programmed death ligand-1 (PD-L1) revolutionizing the therapeutic landscape of advanced non-small cell lung cancer. They were validated initially as second-line treatment, becoming the new standard of care...
January 3, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28057179/biomarqueurs-pr%C3%A3-dictifs-de-r%C3%A3-ponse-aux-traitements-bloquant-les-voies-de-costimulation-inhibitrices
#9
Franck Pagès, Clémence Granier, Amos Kirilovsky, Carine Elsissy, Eric Tartour
Immunotherapies targeting co-inhibitory receptors recently open a new promising approach of cancer treatment. Indeed, an objective clinical response was observed after treatment by anti-CTLA-4 and anti-PD-1 in many indications but the treatment still failed in 70 to 80 % of cases treated. Given the adverse effects and the high cost of these therapies, there is a need for the development of biomarkers. This review focus on potential predictive biomarkers. In peripheral blood, high level of Il-2 soluble receptor at baseline and absence of ICOS+ CD4-T lymphocytes induction may be associated with the absence of clinical response for melanoma patients treated by ipilimumab (anti-CTLA-4)...
November 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/28055269/targeting-pd-1-pathway-a-new-hope-for-gastrointestinal-cancers
#10
Burak Bilgin, Mehmet An Sendur, Muhammed Bülent Akıncı, Didem Şener Dede, Bülent Yalçın
BACKGROUND: VEGF, HER2 and EGFR targeted agents are currently used in gastric, esophageal and colorectal cancers. However, treatment outcomes are still poor in most of the Gastrointestinal (GI) cancers. Immune checkpoints are one of the most promising immunotherapy approaches. In this review article, we aimed to discuss the efficacy and safety of anti-PD-1/PD-L1 therapies in GI cancers, including gastric, esophageal and colorectal cancer in the era of published or reported recent studies...
January 5, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28052005/bortezomib-augments-lymphocyte-stimulatory-cytokine-signaling-in-the-tumor-microenvironment-to-sustain-cd8-t-cell-antitumor-function
#11
Samuel T Pellom, Duafalia F Dudimah, Menaka C Thounaojam, Roman V Uzhachenko, Ashutosh Singhal, Ann Richmond, Anil Shanker
Tumor-induced immune tolerance poses a major challenge for therapeutic interventions aimed to manage cancer. We explored approaches to overcome T-cell suppression in murine breast and kidney adenocarcinomas, and lung fibrosarcoma expressing immunogenic antigens. We observed that treatment with a reversible proteasome inhibitor bortezomib (1 mg/kg body weight) in tumor-bearing mice significantly enhanced the expression of lymphocyte-stimulatory cytokines IL-2, IL-12, and IL-15. Notably, bortezomib administration reduced pulmonary nodules of mammary adenocarcinoma 4T1...
December 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/28049169/management-of-stage-i-and-ii-nonsmall-cell-lung-cancer
#12
Fiona McDonald, Michèle De Waele, Lizza E L Hendriks, Corinne Faivre-Finn, Anne-Marie C Dingemans, Paul E Van Schil
The incidence of stage I and II nonsmall cell lung cancer is likely to increase with the ageing population and introduction of screening for high-risk individuals. Optimal management requires multidisciplinary collaboration. Local treatments include surgery and radiotherapy and these are currently combined with (neo)adjuvant chemotherapy in specific cases to improve long-term outcome. Targeted therapies and immunotherapy may also become important therapeutic modalities in this patient group. For resectable disease in patients with low cardiopulmonary risk, complete surgical resection with lobectomy remains the gold standard...
January 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28039262/potential-predictive-value-of-tp53-and-kras-mutation-status-for-response-to-pd-1-blockade-immunotherapy-in-lung-adenocarcinoma
#13
Zhong-Yi Dong, Wenzhao Zhong, Xu-Chao Zhang, Jian Su, Zhi Xie, Si-Yang Liu, Hai-Yan Tu, Hua-Jun Chen, Yue-Li Sun, Qing Zhou, Jinji Yang, Xuening Yang, Jia-Xin Lin, Honghong Yan, Hao-Ran Zhai, Li-Xu Yan, Ri-Qiang Liao, Si-Pei Wu, Yi-Long Wu
PURPOSE: Although clinical studies have shown promise for targeting programmed cell death protein-1 (PD-1) and ligand (PD-L1) signaling in non-small cell lung cancer (NSCLC), the factors that predict which subtype patients will be responsive to checkpoint blockade are not fully understood. EXPERIMENTAL DESIGN: We performed an integrated analysis on the multiple-dimensional data types including genomic, transcriptomic, proteomic and clinical data from cohorts of lung adenocarcinoma public (Discovery Set) and internal (Validation Set) database and immunotherapeutic patients...
December 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28031719/potential-role-of-immunotherapy-in-advanced-non-small-cell-lung-cancer
#14
REVIEW
Ramon Andrade de Mello, Ana Flávia Veloso, Paulo Esrom Catarina, Sara Nadine, Georgios Antoniou
Immuno checkpoint inhibitors have ushered in a new era with respect to the treatment of advanced non-small-cell lung cancer. Many patients are not suitable for treatment with epidermal growth factor receptor tyrosine kinase inhibitors (eg, gefitinib, erlotinib, and afatinib) or with anaplastic lymphoma kinase inhibitors (eg, crizotinib and ceritinib). As a result, anti-PD-1/PD-L1 and CTLA-4 inhibitors may play a novel role in the improvement of outcomes in a metastatic setting. The regulation of immune surveillance, immunoediting, and immunoescape mechanisms may play an interesting role in this regard either alone or in combination with current drugs...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28029320/pulmonary-infiltrates-in-a-patient-with-advanced-melanoma
#15
Charles A Powell
The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice...
December 28, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28024693/the-race-to-target-met-exon-14-skipping-alterations-in-non-small-cell-lung-cancer-the-why-the-how-the-who-the-unknown-and-the-inevitable
#16
REVIEW
Thanyanan Reungwetwattana, Ying Liang, Viola Zhu, Sai-Hong Ignatius Ou
A number of small molecule tyrosine kinase inhibitors (TKIs) have now been approved for the treatment of non-small cell lung cancers (NSCLC), including those targeted against epidermal growth factor receptor, anaplastic lymphoma kinase, and ROS1. Despite a wealth of agents developed to target the receptor tyrosine kinase, MET, clinical outcomes have as yet been disappointing, leading to pessimism about the role of MET in the pathogenesis of NSCLC. However, in recent years, there has been a renewed interest in MET exon 14 alterations as potential drivers of lung cancer...
January 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28010896/new-perspectives-in-the-second-line-treatment-of-non-squamous-nsclc-patients-results-from-a-large-italian-lung-cancer-working-group
#17
REVIEW
Diego Cortinovis, Vanesa Gregorc, Maria Rita Migliorino, Maria Ida Abate, Anna Manzo, Umberto Malapelle, Alessandro Morabito
Lung cancer is still considered a big killer among cancer diseases, due to high incidence and mortality rates. The newer frontiers of therapeutic development regard the discovery of oncogene driven tumours: however, the majority of NSCLC patients are wild type and they cannot be treated with targeted based agents. The recent positive results obtained with immunotherapy and with the combination of angiogenesis inhibitors and docetaxel, changed the therapeutic scenario of the second line therapy of non squamous NSCLC without actionable mutations...
January 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28003642/car-t-cell-therapy-of-solid-tumors
#18
REVIEW
Carmen S M Yong, Valerie Dardalhon, Christel Devaud, Naomi Taylor, Phillip K Darcy, Michael H Kershaw
The potential for immunotherapy as a treatment option for cancer is clear from remarkable responses of some leukemia patients to adoptive cell transfer using autologous T cells genetically modified to express chimeric antigen receptors (CARs). However, the vast majority of cancers, in particular the more common solid cancers, such as those of the breast, colon and lung, fail to respond significantly to infusions of CAR T cells. Solid cancers present some formidable barriers to adoptive cell transfer, including suppression of T cell function and inhibition of T cell localization...
December 22, 2016: Immunology and Cell Biology
https://www.readbyqxmd.com/read/27999750/reprogramming-the-lung-microenvironment-by-inhaled-immunotherapy-fosters-immune-destruction-of-tumor
#19
Valentino Le Noci, Michele Sommariva, Monica Tortoreto, Nadia Zaffaroni, Manuela Campiglio, Elda Tagliabue, Andrea Balsari, Lucia Sfondrini
Due to their constant exposure to inhaled antigens, lungs represent a particularly immunosuppressive environment that limits excessive immune responses; however, cancer cells can exploit this unique environment for their growth. We previously described the ability of aerosolized CpG-ODN combined with Poly(I:C) (TLR9 and TLR3 agonists, respectively) to promote antitumor immunity in a B16 melanoma lung metastasis model. Here, we explored the possibility of improving the therapeutic efficacy of TLR9/TLR3 agonist combinations by including in the inhalant either an antibody directed to both Ly6G and Ly6C markers to locally deplete myeloid-derived suppressive cells (MDSCs) or IFNα to directly activate the natural killer (NK) and macrophage innate immune cells in the lung...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27990082/european-society-for-medical-oncology-2016-congress
#20
Walter Alexander
We review several key sessions from the European Society for Medical Oncology's annual congress, including those on emerging immunotherapies for melanoma and non-small-cell lung cancer and on treatments for renal, ovarian, and breast cancer.
December 2016: P & T: a Peer-reviewed Journal for Formulary Management
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