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https://www.readbyqxmd.com/read/27923825/rational-selection-of-syngeneic-preclinical-tumor-models-for-immunotherapeutic-drug-discovery
#1
Suzanne I S Mosely, John E Prime, Richard C A Sainson, Jens-Oliver Koopmann, Dennis Y Q Wang, Danielle M Greenawalt, Miika J Ahdesmaki, Rebecca Leyland, Stefanie Mullins, Luciano Pacelli, Danielle Marcus, Judith Anderton, Amanda Watkins, Jane Coates Ulrichsen, Philip Brohawn, Brandon W Higgs, Matthew McCourt, Hazel Jones, James A Harper, Michelle Morrow, Viia Valge-Archer, Ross Stewart, Simon J Dovedi, Robert W Wilkinson
Murine syngeneic tumor models are critical to novel immuno-based therapy development but the molecular and immunological features of these models are still not clearly defined. The translational relevance of differences between the models is not fully understood, impeding appropriate preclinical model selection for target validation, and ultimately hindering drug development. Across a panel of commonly-used murine syngeneic tumor models, we showed variable responsiveness to immunotherapies. We employed array comparative genomic hybridization, whole-exome sequencing, exon microarray analysis, and flow cytometry to extensively characterize these models, which revealed striking differences that may underlie these contrasting response profiles...
December 6, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27846884/future-perspectives-in-melanoma-research-meeting-report-from-the-melanoma-bridge-napoli-december-1st-4th-2015
#2
Paolo A Ascierto, Sanjiv Agarwala, Gerardo Botti, Alessandra Cesano, Gennaro Ciliberto, Michael A Davies, Sandra Demaria, Reinhard Dummer, Alexander M Eggermont, Soldano Ferrone, Yang Xin Fu, Thomas F Gajewski, Claus Garbe, Veronica Huber, Samir Khleif, Michael Krauthammer, Roger S Lo, Giuseppe Masucci, Giuseppe Palmieri, Michael Postow, Igor Puzanov, Ann Silk, Stefani Spranger, David F Stroncek, Ahmad Tarhini, Janis M Taube, Alessandro Testori, Ena Wang, Jennifer A Wargo, Cassian Yee, Hassane Zarour, Laurence Zitvogel, Bernard A Fox, Nicola Mozzillo, Francesco M Marincola, Magdalena Thurin
The sixth "Melanoma Bridge Meeting" took place in Naples, Italy, December 1st-4th, 2015. The four sessions at this meeting were focused on: (1) molecular and immune advances; (2) combination therapies; (3) news in immunotherapy; and 4) tumor microenvironment and biomarkers. Recent advances in tumor biology and immunology has led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS) of cancer patients. Immunotherapies in particular have emerged as highly successful approaches to treat patients with cancer including melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin's disease...
November 15, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27792052/novel-insights-in-the-regulation-and-function-of-macrophages-in-the-tumor-microenvironment
#3
Evangelia Bolli, Kiavash Movahedi, Damya Laoui, Jo A Van Ginderachter
PURPOSE OF REVIEW: Tumors contain not only cancer cells but also nontransformed types of cells, the stromal cells. A bidirectional interplay exists between transformed and nontransformed cells leading to tumor progression and metastasis. Tumor-associated macrophages (TAMs) are the most abundant tumor-infiltrating leukocytes characterized by a high heterogeneity and plasticity. TAMs exhibit strong protumoral activities and are related to bad prognosis and worse overall survival in various cancer types...
January 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/27789023/the-evolution-of-oncology-companion-diagnostics-from-signal-transduction-to-immuno-oncology
#4
REVIEW
Nicholas C Dracopoli, Mark S Boguski
Sixteen oncology drugs have been approved with a companion diagnostic (CDx) test by the FDA. These represent only 9.6% of the 167 oncology drug approvals since 1998, the year the first CDx test for Herceptin was approved. The great majority of CDx tests are for drugs that inhibit signal transduction pathways by either inhibiting the intracellular kinase activity with a small molecule or preventing ligand-induced receptor activation with a monoclonal antibody. In most of these cases, prospective patient selection for the biomarker-positive subpopulation was initiated in or before Phase II...
October 24, 2016: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/27783034/aptamers-a-new-technological-platform-in-cancer-immunotherapy
#5
REVIEW
Fernando Pastor
The renaissance of cancer immunotherapy is, nowadays, a reality. In the near future, it will be very likely among the first-line treatments for cancer patients. There are several different approaches to modulate the immune system to fight against tumor maladies but, so far, monoclonal antibodies may currently be the most successful immuno-tools used to that end. The number of ongoing clinical trials with monoclonal antibodies has been increasing exponentially over the last few years upon the Food and Drug Administration (FDA) approval of the first immune-checkpoint blockade antibodies...
October 24, 2016: Pharmaceuticals
https://www.readbyqxmd.com/read/27777979/the-head-and-neck-cancer-immune-landscape-and-its-immunotherapeutic-implications
#6
Rajarsi Mandal, Yasin Şenbabaoğlu, Alexis Desrichard, Jonathan J Havel, Martin G Dalin, Nadeem Riaz, Ken-Wing Lee, Ian Ganly, A Ari Hakimi, Timothy A Chan, Luc G T Morris
Recent clinical trials have demonstrated a clear survival advantage in advanced head and neck squamous cell carcinoma (HNSCC) patients treated with immune checkpoint blockade. These emerging results reveal that HNSCC is one of the most promising frontiers for immunotherapy research. However, further progress in head and neck immuno-oncology will require a detailed understanding of the immune infiltrative landscape found in these tumors. We leveraged transcriptome data from 280 tumors profiled by The Cancer Genome Atlas (TCGA) to comprehensively characterize the immune landscape of HNSCC in order to develop a rationale for immunotherapeutic strategies in HNSCC and guide clinical investigation...
October 20, 2016: JCI Insight
https://www.readbyqxmd.com/read/27742649/next-steps-in-immuno-oncology-enhancing-antitumor-effects-through-appropriate-patient-selection-and-rationally-designed-combination-strategies
#7
A K S Salama, S J Moschos
BACKGROUND: Cancers escape immune surveillance via distinct mechanisms that involve central (negative selection within the thymus) or peripheral (lack of costimulation, receipt of death/anergic signals by tumor, immunoregulatory cell populations) immune tolerance. During the 1990s, moderate clinical benefit was seen using several cytokine therapies for a limited number of cancers. Over the past 20 years, extensive research has been performed to understand the role of various components of peripheral immune tolerance, with the co-inhibitory immune checkpoint molecules cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1), and its ligand (PD-L1) being the most well characterized at preclinical and clinical levels...
October 13, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27714433/tumor-directed-immunotherapy-can-generate-tumor-specific-t-cell-responses-through-localized-co-stimulation
#8
Peter Ellmark, Sara M Mangsbo, Christina Furebring, Per Norlén, Thomas H Tötterman
The most important goals for the field of immuno-oncology are to improve the response rate and increase the number of tumor indications that respond to immunotherapy, without increasing adverse side effects. One approach to achieve these goals is to use tumor-directed immunotherapy, i.e., to focus the immune activation to the most relevant part of the immune system. This may improve anti-tumor efficacy as well as reduce immune-related adverse events. Tumor-directed immune activation can be achieved by local injections of immune modulators in the tumor area or by directing the immune modulator to the tumor using bispecific antibodies...
October 6, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27663482/immuno-pharmacodynamics-for-evaluating-mechanism-of-action-and-developing-immunotherapy-combinations
#9
REVIEW
Ralph E Parchment, Andrea Regier Voth, James H Doroshow, Jay A Berzofsky
Immunotherapy has become a major modality of cancer treatment, with multiple new classes of immunotherapeutics recently entering the clinic and obtaining market approval from regulatory agencies. While the promise of these therapies is great, so is the number of possible combinations not only with each other but also with small molecule therapeutics. Furthermore, the observation of unusual dose-response relationships suggests a critical dependency of drug effectiveness on the dosage regimen (dose and schedule)...
August 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/27650038/immunoscore-and-immunoprofiling-in-cancer-an-update-from-the-melanoma-and-immunotherapy-bridge-2015
#10
J Galon, B A Fox, C B Bifulco, G Masucci, T Rau, G Botti, F M Marincola, G Ciliberto, F Pages, P A Ascierto, M Capone
The fifth "Melanoma Bridge Meeting" took place in Naples, December 1-5th, 2015. The main topics discussed at this meeting were: Molecular and Immuno advances, Immunotherapies and Combination Therapies, Tumor Microenvironment and Biomarkers and Immunoscore. The natural history of cancer involves interactions between the tumor and the immune system of the host. The immune infiltration at the tumor site may be indicative of host response. Significant correlations were shown between the levels of immune cell infiltration in tumors and patient's clinical outcome...
2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27622044/large-scale-microarray-profiling-reveals-four-stages-of-immune-escape-in-non-hodgkin-lymphomas
#11
Marie Tosolini, Christelle Algans, Frédéric Pont, Bernard Ycart, Jean-Jacques Fournié
Non-Hodgkin B-cell lymphoma (B-NHL) are aggressive lymphoid malignancies that develop in patients due to oncogenic activation, chemo-resistance, and immune evasion. Tumor biopsies show that B-NHL frequently uses several immune escape strategies, which has hindered the development of checkpoint blockade immunotherapies in these diseases. To gain a better understanding of B-NHL immune editing, we hypothesized that the transcriptional hallmarks of immune escape associated with these diseases could be identified from the meta-analysis of large series of microarrays from B-NHL biopsies...
July 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27610200/adoptive-cell-therapy-and-modulation-of-the-tumour-microenvironment-new-insights-from-asco-2016
#12
EDITORIAL
Leila Khoja, Bishal Gyawali
Immuno-oncology has changed the landscape of cancer treatment in recent years. Immune checkpoint inhibitors (ICI) have shown survival advantage with long term remissions in a variety of cancers. However, there is another approach to harnessing the power of the immune system in combating cancer: the adoptive cell therapy (ACT) strategy. Although ACT is restricted to small specialized centres and has yet to deliver as much success as ICI, some important results were presented at this year's ASCO meeting. Important lessons have been learned from these studies, including the prospects and challenges ahead...
2016: Ecancermedicalscience
https://www.readbyqxmd.com/read/27557809/antibody-engineering-therapeutics-2016-the-antibody-society-s-annual-meeting-december-11-15-2016-san-diego-ca
#13
James W Larrick, Mark R Alfenito, Jamie K Scott, Paul W H I Parren, Dennis R Burton, Andrew R M Bradbury, Cynthia A Lemere, Anne Messer, James S Huston, Paul J Carter, Trudi Veldman, Kerry A Chester, Janine Schuurman, Gregory P Adams, Janice M Reichert
Antibody Engineering & Therapeutics, the largest meeting devoted to antibody science and technology and the annual meeting of The Antibody Society, will be held in San Diego, CA on December 11-15, 2016. Each of 14 sessions will include six presentations by leading industry and academic experts. In this meeting preview, the session chairs discuss the relevance of their topics to current and future antibody therapeutics development. Session topics include bispecifics and designer polyclonal antibodies; antibodies for neurodegenerative diseases; the interface between passive and active immunotherapy; antibodies for non-cancer indications; novel antibody display, selection and screening technologies; novel checkpoint modulators / immuno-oncology; engineering antibodies for T-cell therapy; novel engineering strategies to enhance antibody functions; and the biological Impact of Fc receptor engagement...
August 24, 2016: MAbs
https://www.readbyqxmd.com/read/27458526/immuno-oncology-combinations-raising-the-tail-of-the-survival-curve
#14
Samuel J Harris, Jessica Brown, Juanita Lopez, Timothy A Yap
There have been exponential gains in immuno-oncology in recent times through the development of immune checkpoint inhibitors. Already approved by the U.S. Food and Drug Administration for advanced melanoma and non-small cell lung cancer, immune checkpoint inhibitors also appear to have significant antitumor activity in multiple other tumor types. An exciting component of immunotherapy is the durability of antitumor responses observed, with some patients achieving disease control for many years. Nevertheless, not all patients benefit, and efforts should thus now focus on improving the efficacy of immunotherapy through the use of combination approaches and predictive biomarkers of response and resistance...
June 2016: Cancer Biology & Medicine
https://www.readbyqxmd.com/read/27441513/update-on-new-therapies-with-immune-checkpoint-inhibitors
#15
Jennifer J Peterson, Susan K Steele-Moses
BACKGROUND: Immunotherapy has had a long history in cancer treatment and, with recent breakthroughs, new drugs are available that have shown promising results. OBJECTIVES: The current article discusses an overview of immune function, including immunoediting and the theory of immune checkpoints, as well as specific drugs that have been approved as immune checkpoint inhibitors. Additional discussion includes a review of nursing implications and administration, side effects, adverse events, and the future of immuno-oncology...
August 1, 2016: Clinical Journal of Oncology Nursing
https://www.readbyqxmd.com/read/27429658/immunotherapy-for-head-and-neck-squamous-cell-carcinoma
#16
Thorsten Fuereder
Over the past years immuno-oncology has evolved and become a novel promising strategy for cancer therapy. Immune checkpoint inhibitors such as pembrolizumab or nivolumab, which target the interaction between programmed death receptor 1/programmed death ligand 1 (PD-1/PDL-1) and PDL-2, have been recently approved for the treatment of various malignancies and are currently being investigated in clinical phase III trials for head and neck squamous cell carcinoma (HNSCC). Data available from these trials indicate substantial activity accompanied by a favorable safety and toxicity profile in this patient population...
2016: Memo
https://www.readbyqxmd.com/read/27373242/immune-checkpoint-inhibitors-a-milestone-in-the-treatment-of-melanoma
#17
REVIEW
Sophia M Wilden, Berenice M Lang, Peter Mohr, Stephan Grabbe
It has been known for decades that the immune system is able to detect and destroy tumor cells. In the past, this knowledge - mostly acquired through animal experiments - could not be used to benefit our patients, because immuno-oncological therapeutic approaches in humans had constantly failed over recent decades. With the exception of adjuvant interferon therapy, none of these approaches had found its way into everyday clinical practice, and only very few patients were able to enjoy long-term survival associated with good quality of life...
July 2016: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
https://www.readbyqxmd.com/read/27363491/standardized-evaluation-of-tumor-infiltrating-lymphocytes-in-breast-cancer-results-of-the-ring-studies-of-the-international-immuno-oncology-biomarker-working-group
#18
Carsten Denkert, Stephan Wienert, Audrey Poterie, Sibylle Loibl, Jan Budczies, Sunil Badve, Zsuzsanna Bago-Horvath, Anita Bane, Shahinaz Bedri, Jane Brock, Ewa Chmielik, Matthias Christgen, Cecile Colpaert, Sandra Demaria, Gert Van den Eynden, Giuseppe Floris, Stephen B Fox, Dongxia Gao, Barbara Ingold Heppner, S Rim Kim, Zuzana Kos, Hans H Kreipe, Sunil R Lakhani, Frederique Penault-Llorca, Giancarlo Pruneri, Nina Radosevic-Robin, David L Rimm, Stuart J Schnitt, Bruno V Sinn, Peter Sinn, Nicolas Sirtaine, Sandra A O'Toole, Giuseppe Viale, Koen Van de Vijver, Roland de Wind, Gunter von Minckwitz, Frederick Klauschen, Michael Untch, Peter A Fasching, Toralf Reimer, Karen Willard-Gallo, Stefan Michiels, Sherene Loi, Roberto Salgado
Multiple independent studies have shown that tumor-infiltrating lymphocytes (TIL) are prognostic in breast cancer with potential relevance for response to immune-checkpoint inhibitor therapy. Although many groups are currently evaluating TIL, there is no standardized system for diagnostic applications. This study reports the results of two ring studies investigating TIL conducted by the International Working Group on Immuno-oncology Biomarkers. The study aim was to determine the intraclass correlation coefficient (ICC) for evaluation of TIL by different pathologists...
October 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27332557/therapeutic-strategies-in-diseases-of-the-digestive-tract-2015-and-beyond-targeted-therapies-in-colon-cancer-today-and-tomorrow
#19
Michael Pohl, Wolff Schmiegel
BACKGROUND: Colorectal cancer (CRC) is the third most common cancer type in Western countries. Significant progress has been made in the last decade in the therapy of metastatic CRC (mCRC) with a median overall survival (OS) of patients exceeding 30 months. The integration of biologic targeted therapies and anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MABs) in the treatment of patients with genomically selected all-RAS wild-type mCRC leads to a significant progress in advanced incurable disease state...
2016: Digestive Diseases
https://www.readbyqxmd.com/read/27330803/immune-related-response-evaluations-during-immune-checkpoint-inhibitor-therapy-establishing-a-common-language-for-the-new-arena-of-cancer-treatment
#20
Mizuki Nishino
The recent study by Hodi et al. published in the Journal of Clinical Oncology has evaluated unconventional response patterns during PD-1 inhibitor therapy using immune-related response criteria (irRC) in comparison with RECIST1.1, which constitutes an important step to further understand immune-related response phenomena. This commentary discusses the key observations in the study in terms of their implications and pitfalls, and describes unmet needs that remain to be addressed. The article also emphasizes the important role of tumor response criteria as a "common language" to describe the results of cancer treatment, and discusses future directions for further advances of the field of immuno-oncology...
2016: Journal for Immunotherapy of Cancer
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