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Immunotherapy In Lung Cancer

Win Sen Heng, Reinoud Gosens, Frank A E Kruyt
Lung cancer remains the leading cause of cancer-related deaths despite recent breakthroughs in immunotherapy. The widely embraced cancer stem cell (CSC) theory has also been applied for lung cancer, postulating that an often small proportion of tumor cells with stem cell properties are responsible for tumor growth, therapeutic resistance and metastasis. The identification of these CSCs and underlying molecular maintenance mechanisms is considered to be absolutely necessary for developing therapies for their riddance, hence achieving remission...
December 14, 2018: Biochemical Pharmacology
Ahmed Mohieldin, Ayman Rasmy, Mohamed Ashour, Muath Al-Nassar, Rola H Ali, Fahad G El-Enezi
Introduction: Lung cancer is the leading cause of cancer mortality worldwide, despite advances in management, especially with targeted agents and immunotherapy. Numerous oncogenes have been identified that control the growth of these malignancies. Anaplastic lymphoma kinase (ALK) is a tyrosine kinase that develops distorted functioning as a result of chromosomal rearrangement. Crizotinib, a tyrosine kinase inhibitor (TKI), was approved by the Food and Drug Administration (FDA) in 2011 for the treatment of advanced ALK-positive non-small-cell lung cancer (NSCLC)...
2018: Cancer Management and Research
Zheng Xiao, Cheng-Qiong Wang, Ji-Hong Feng, Ming-Hua Zhou, Yu-Zhi Wang, Na-Na Li, Yong-Ping Sun, Shi-Yu Liu, Xin-Sheng Yao, Cheng-Wen Li, Bin Ma, Jie Ding, Ling Chen
BACKGROUND AIMS: Cytokine-induced killer (CIK) cells are the most commonly used cellular immunotherapy for multiple tumors. To further confirm whether chemotherapy with CIK cells improves clinical effectiveness and to reveal its optimal use in non-small cell lung cancer (NSCLC), we systematically reevaluated all relevant studies. METHODS: We collected all studies about chemotherapy with CIK cells for NSCLC from the Medline, Embase, Web of Science, China National Knowledge Infrastructure Database (CNKI), Chinese Scientific Journals Full-Text Database (VIP), Wanfang Data, China Biological Medicine Database (CBM), Cochrane Central Register of Controlled Trials (CENTRAL), Chinese clinical trial registry (Chi-CTR), World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and U...
December 14, 2018: Cytotherapy
Nicolas Marcoux, Scott N Gettinger, Grainne O'Kane, Kathryn C Arbour, Joel W Neal, Hatim Husain, Tracey L Evans, Julie R Brahmer, Alona Muzikansky, Philip D Bonomi, Salvatore Del Prete, Anna Wurtz, Anna F Farago, Dora Dias-Santagata, Mari Mino-Kenudson, Karen L Reckamp, Helena A Yu, Heather A Wakelee, Frances A Shepherd, Zofia Piotrowska, Lecia V Sequist
PURPOSE: Approximately 3% to 10% of EGFR (epidermal growth factor receptor) -mutant non-small cell lung cancers (NSCLCs) undergo transformation to small-cell lung cancer (SCLC), but their clinical course is poorly characterized. METHODS: We retrospectively identified patients with EGFR-mutant SCLC and other high-grade neuroendocrine carcinomas seen at our eight institutions. Demographics, disease features, and outcomes were analyzed. RESULTS: We included 67 patients-38 women and 29 men; EGFR mutations included exon 19 deletion (69%), L858R (25%), and other (6%)...
December 14, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Hakan Köksal, Elisabeth Müller, Else Marit Inderberg, Øyvind Bruland, Sébastien Wälchli
Novel therapies to treat patients with solid cancers that have developed resistance to chemotherapy represent unmet needs of considerable dimensions. In the present review, we will address the attempts to develop Chimeric Antigen Receptor (CAR) targeted immunotherapy against osteosarcoma (OS). This aggressive cancer displays its peak incidence in children and young adults. The main cause of patient death is lung metastases with a 5-year survival as low as 5-10% in the primary metastatic setting and 30% in the relapse situation, respectively...
December 14, 2018: Scandinavian Journal of Immunology
Ruocong Zhao, Lin Cheng, Zhiwu Jiang, Xinru Wei, Baiheng Li, Qiting Wu, Suna Wang, Simiao Lin, Youguo Long, Xuchao Zhang, Yilong Wu, Xin Du, Duanqing Pei, Pentao Liu, Yangqiu Li, Shuzhong Cui, Yao Yao, Peng Li
Chimeric antigen receptor (CAR) T cell immunotherapies have shown remarkable efficacy in treating multiple types of hematological malignancies but are not sufficiently effective at treating solid tumors. NKG2D is a strong activating receptor for NK cells and a co-stimulatory receptor for T cells. NKG2D signal transduction depends on DNAX-activating protein 10 (DAP10). Here, we introduced the cytoplasmic domain of DAP10 into the second-generation CARs M28z and G28z to generate M28z10 and G28z10, which target mesothelin (MSLN) and glypican 3 (GPC3), respectively...
2019: Oncoimmunology
Dipesh Uprety
No abstract text is available yet for this article.
November 22, 2018: Clinical Lung Cancer
Arturo Navarro-Martín, Isabel Linares Galiana, Miguel A Berenguer Frances, Jon Cacicedo, Rut Cañas Cortés, Silvia Comas Anton, Susana Padrones Sánchez, Santiago Bolívar Cuevas, Renate Parry, Ferran Guedea Edo
An immunophenotyping analysis was performed in peripheral blood samples from seven patients with lung cancer unfit for surgery treated with stereotactic body radiotherapy (SBRT). The objective was to characterize the effect of SBRT on the host immune system. Four patients received 60 Gy (7.5 Gy × 8) and three 50 Gy (12.5 Gy × 4). Analyses were performed before SBRT, 72 h after SBRT, and at one, three, and six months after the end of SBRT. Of note, there was a specific increase of the immunoactive component of the immune system, with elevation of CD56+high CD16+ natural killer (NK) cells (0...
December 9, 2018: International Journal of Molecular Sciences
Ping-Chih Hsu, Cheng-Ta Yang, David M Jablons, Liang You
The programmed death-ligand 1(PD-L1)/PD-1 pathway is an immunological checkpoint in cancer cells. The binding of PD-L1 and PD-1 promotes T-cell tolerance and helps tumor cells escape from host immunity. Immunotherapy targeting the PD-L1/PD-1 axis has been developed as an anti-cancer therapy and used in treating advanced human non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM). Yes-associated protein (YAP) is a key mediator of the Hippo/YAP signaling pathway, and plays important roles in promoting cancer development, drug resistance and metastasis in human NSCLC and MPM...
December 7, 2018: Biomedicines
Xiaoli Liu, Huaimin Liu, Suxia Luo
RATIONALE: For metastatic non-small cell lung cancer with no epidermal growth factor receptor mutations or anaplastic lymphoma kinase gene rearrangements, programmed cell death-1 (PD-1) blockade is preferentially recommended post first-line chemotherapy. However, still many patients do not respond to these agents. After development of resistance to PD-1 blockade, further evaluation of chemotherapy regimen will be necessary. PATIENT CONCERNS: A 57-year old man had cough with minimal whitish expectoration...
December 2018: Medicine (Baltimore)
Steven D Criss, Meghan J Mooradian, Deirdre F Sheehan, Leyre Zubiri, Melissa A Lumish, Justin F Gainor, Kerry L Reynolds, Chung Yin Kong
Importance: In early 2018, durvalumab became the first immunotherapy to be approved for adjuvant treatment of patients with unresectable stage III non-small cell lung cancer (NSCLC) whose cancer has not progressed after definitive chemoradiotherapy. However, the cost-effectiveness and potential economic implications of using this high-priced therapy in this indication are unknown to date. Objective: To explore the cost-effectiveness and potential budgetary consequences of durvalumab consolidation therapy vs no consolidation therapy after chemoradiotherapy in stage III NSCLC in the context of the US health care system...
December 13, 2018: JAMA Oncology
Valsamo Anagnostou, Patrick M Forde, James R White, Noushin Niknafs, Carolyn Hruban, Jarushka Naidoo, Kristen A Marrone, I K Ashok Sivakumar, Daniel C Bruhm, Samuel Rosner, Jillian Phallen, Alessandro Leal, Vilmos Adleff, Kellie N Smith, Tricia R Cottrell, Lamia Rhymee, Doreen N Palsgrove, Christine L Hann, Benjamin Levy, Josephine Feliciano, Christos Georgiades, Franco Verde, Peter Illei, Qing Kay Li, Edward Gabrielson, Malcolm V Brock, James M Isbell, Jennifer L Sauter, Janis Taube, Robert B Scharpf, Rachel Karchin, Drew M Pardoll, Jamie E Chaft, Matthew D Hellmann, Julie R Brahmer, Victor E Velculescu
Despite the initial successes of immunotherapy, there is an urgent clinical need for molecular assays that identify patients more likely to respond. Here we report that ultrasensitive measures of circulating tumor DNA (ctDNA) and T cell expansion can be used to assess responses to immune checkpoint blockade in metastatic lung cancer patients (N=24). Patients with clinical response to therapy had a complete reduction in ctDNA levels after initiation of therapy whereas, non-responders had no significant changes or an increase in ctDNA levels...
December 12, 2018: Cancer Research
Lucas C Adam, Junaid Raja, Johannes M Ludwig, Adebowale Adeniran, Scott N Gettinger, Hyun S Kim
Novel approaches with checkpoint inhibitors in immunotherapy continue to be essential in the treatment of non-small cell lung cancer (NSCLC). However, the low rate of primary response and the development of acquired resistance during the immunotherapy limit their long-term effectiveness. The underlying cause of acquired resistance is poorly understood; potential management strategies for patients with acquired resistance are even less clear. Here, we report the case of a 75-year-old female smoker with cough, fatigue, and weight loss that was found to have an 8...
December 12, 2018: Journal for Immunotherapy of Cancer
Luis Corrales, Katherine Scilla, Christian Caglevic, Ken Miller, Julio Oliveira, Christian Rolfo
The management of Non-Small Cell Lung Cancer (NSCLC) has changed dramatically in the last 10 years with an increase in the understanding of the biology and with the development of new and multiple treatments. Chemotherapy being the first systemic treatment used in the setting of advanced disease, proving benefit for patients over palliative care. With the identification of oncogenic drivers, innovative targeted therapies were developed and tested, leading to important changes in the management of certain patients and giving to some of them the possibility to be treated in first line with oral inhibitors...
2018: Advances in Experimental Medicine and Biology
Alba Gonzalez-Junca, Kyla Driscoll, Ilenia Pellicciotta, Shisuo Du, Chen Hao Lo, Ritu Roy, Renate Parry, Iliana Tenvooren, Diana Marquez, Matthew H Spitzer, Mary Helen Barcellos-Hoff
Transforming growth factor β (TGFβ) is an effector of immune suppression and contributes to a permissive tumor microenvironment that compromises effective immunotherapy. We identified a correlation between TGFB1 and genes expressed by myeloid cells, but not granulocytes, in TCGA lung adenocarcinoma data, in which high TGFB1 expression was associated with poor survival. To determine whether TGFβ affected cell fate decisions and lineage commitment, we studied primary cultures of CD14+ monocytes isolated from peripheral blood of healthy donors...
December 11, 2018: Cancer Immunology Research
Cecilia Orbegoso, Krithika Murali, Susana Banerjee
Immunotherapy has been proven effective in several tumours, hence diverse immune checkpoint inhibitors are currently licensed for the treatment of melanoma, kidney cancer, lung cancer and most recently, tumours with microsatellite instability. There is much enthusiasm for investigating this approach in gynaecological cancers and the possibility that immunotherapy might become part of the therapeutic landscape for gynaecological malignancies. Cervical cancer is the fourth most frequent cancer in women worldwide and represents 7...
November 2018: Reports of Practical Oncology and Radiotherapy
Chien-Chun Steven Pai, Donald M Simons, Xiaoqing Lu, Michael Evans, Junnian Wei, Yung-Hua Wang, Mingyi Chen, John Huang, Chanhyuk Park, Anthony Chang, Jiaxi Wang, Susan Westmoreland, Christine Beam, Dave Banach, Diana Bowley, Feng Dong, Jane Seagal, Wendy Ritacco, Paul L Richardson, Soumya Mitra, Grace Lynch, Pete Bousquet, John Mankovich, Gillian Kingsbury, Lawrence Fong
While immune checkpoint blockade leads to potent antitumor efficacy, it also leads to immune-related adverse events in cancer patients. These toxicities stem from systemic immune activation resulting in inflammation of multiple organs, including the gastrointestinal tract, lung, and endocrine organs. We developed a dual variable domain immunoglobulin of anti-CTLA4 antibody (anti-CTLA4 DVD, where CTLA4 is defined as cytotoxic T lymphocyte-associated antigen-4) possessing an outer tumor-specific antigen-binding site engineered to shield the inner anti-CTLA4-binding domain...
December 10, 2018: Journal of Clinical Investigation
James Chih-Hsin Yang, Shirish M Gadgeel, Lecia Van Dam Sequist, Chien-Liang Wu, Vassiliki A Papadimitrakopoulou, Wu-Chou Su, Joseph Fiore, Sanatan Saraf, Harry Raftopoulos, Amita Patnaik
INTRODUCTION: Anti-EGFR agents are standard treatments for patients with EGFR-mutant advanced NSCLC. The feasibility of combining erlotinib or gefitinib with anti-PD1 immunotherapy pembrolizumab was evaluated in the phase 1/2 KEYNOTE-021 (NCT02039674) study. METHODS: Adults with previously untreated stage IIIB/IV EGFR-mutant NSCLC were treated with pembrolizumab 2 mg/kg IV every 3 weeks plus oral erlotinib 150 mg daily in cohort E or oral gefitinib 250 mg daily in cohort F, using a 3+3 design with cohort expansion...
December 4, 2018: Journal of Thoracic Oncology
Luca G Campana, Ibrahim Edhemovic, Declan Soden, Anna M Perrone, Marco Scarpa, Laura Campanacci, Maja Cemazar, Sara Valpione, Damijan Miklavčič, Simone Mocellin, Elisabetta Sieni, Gregor Sersa
The treatment of tumors with electrochemotherapy (ECT) has surged over the past decade. Thanks to the transient cell membrane permeabilization induced by the short electric pulses used by ECT, cancer cells are exposed to otherwise poorly permeant chemotherapy agents, with consequent increased cytotoxicity. The codification of the procedure in 2006 led to a broad diffusion of the procedure, mainly in Europe, and since then, the progressive clinical experience, together with the emerging technologies, have extended the range of its application...
December 1, 2018: European Journal of Surgical Oncology
Jie Liang, Gertrud Maria Hänsch, Katrin Hübner, Yvonne Samstag
Sulforaphane (SFN) is a naturally occurring isothiocyanate derived from cruciferous vegetables such as broccoli. It has been reported to inhibit the growth of a variety of cancers, such as breast, prostate, colon, skin, lung, gastric or bladder cancer. SFN is supposed to act primarily as an antioxidant due to the activation of the Nrf2-Keap1 signaling pathway. This enhances the activity of phase II detoxifying enzymes and the trapping of free radicals. Finally, SFN induces cell cycle arrest or apoptosis of tumor cells...
November 22, 2018: Advances in Biological Regulation
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