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https://www.readbyqxmd.com/read/28938090/small-molecule-targets-in-immuno-oncology
#1
REVIEW
Dashyant Dhanak, James P Edwards, Ancho Nguyen, Peter J Tummino
Advances in understanding the role and molecular mechanisms underlying immune surveillance and control of (pre)malignancies is revolutionizing clinical practice in the treatment of cancer. Presently, multiple biologic drugs targeting the immune checkpoint proteins PD(L)1 or CTLA4 have been approved and/or are in advanced stages of clinical development for many cancers. In addition, combination therapy with these agents and other immunomodulators is being intensively explored with the aim of improving primary response rates or prolonging overall survival...
September 21, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28937974/high-somatic-mutation-and-neoantigen-burden-are-correlated-with-decreased-progression-free-survival-in-multiple-myeloma
#2
A Miller, Y Asmann, L Cattaneo, E Braggio, J Keats, D Auclair, S Lonial, S J Russell, A K Stewart
Tumor-specific mutations can result in immunogenic neoantigens, both of which have been correlated with responsiveness to immune checkpoint inhibitors in highly mutagenic cancers. However, early results of single-agent checkpoint inhibitors in multiple myeloma (MM) have been underwhelming. Therefore, we sought to understand the relationship between mutation and neoantigen landscape of MM patients and responsiveness to therapies. Somatic mutation burden, neoantigen load, and response to therapy were determined using interim data from the MMRF CoMMpass study (NCT01454297) on 664 MM patients...
September 22, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28937963/ki67-and-lymphocytes-in-the-pretherapeutic-core-biopsy-of-primary-invasive-breast-cancer-positive-markers-of-therapy-response-prediction-and-superior-survival
#3
REVIEW
Claus M Schlotter, Lothar Tietze, Ulf Vogt, Carlos Villena Heinsen, Antje Hahn
Background Core needle biopsy plays a crucial role as diagnostic tool for BC. Both Ki67 and likely tumor-infiltrating lymphocytes (TILs) in the near future are determining the kind of systemic therapy. The role of TILs in BC is still an issue for clinical research, albeit preliminary results of neoadjuvant and adjuvant clinical studies already now highlight the crucial impact of TILs on therapy response and survival. Methods Evaluation of related publications (pubmed) and meeting abstracts (ASCO, SABCS). Results The monoclonal antibody Ki67 recognizing a nuclear antigene in proliferating cells is a positive marker of therapy response and superior survival...
September 22, 2017: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/28937681/primary-t-cells-for-mrna-mediated-immunotoxin-delivery
#4
R Eggers, A Philippi, M O Altmeyer, F Breinig, M J Schmitt
Immune cells become increasingly attractive as delivery system for immunotoxins in cancer therapy in order to reduce the intrinsic toxicity and severe side effects of chimeric protein toxins. In this study, we investigated the potential of human primary T cells to deliver a secreted immunotoxin through transient mRNA transfection. The chimeric protein toxin was directed towards the neovasculature of cancer cells by fusing a truncated version of Pseudomonas exotoxin A (PE38) to human vascular endothelial growth factor (VEGF) and to the single chain variable fragment (scFv) of anti-Her2/neu...
September 22, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28936747/exosomes-outlook-for-future-cell-free-cardiovascular-disease-therapy
#5
Bahar Barani, Sheeja Rajasingh, Johnson Rajasingh
Cardiovascular diseases are the number one cause of death globally with an estimated 7.4 million people dying from coronary heart disease. Studies have been conducted to identify the therapeutic utility of exosomes in many diseases, including cardiovascular diseases. It has been demonstrated that exosomes are immune modulators, can be used to treat cardiac ischemic injury, pulmonary hypertension and many other diseases, including cancers. Exosomes can be used as a biomarker for disease and cell-free drug delivery system for targeting the cells...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28936716/induction-of-reactive-oxygen-species-an-emerging-approach-for-cancer-therapy
#6
REVIEW
Zhengzhi Zou, Haocai Chang, Haolong Li, Songmao Wang
Reactive oxygen species (ROS), a group of ions and molecules, include hydroxyl radicals (·OH), alkoxyl radicals, superoxide anion (O2·-), singlet oxygen ((1)O2) and hydrogen peroxide (H2O2). Hydroxyl radicals and alkoxyl radicals are extremely and highly reactive species respectively. Endogenous ROS are mainly formed in mitochondrial respiratory chain. Low levels of ROS play important roles in regulating biological functions in mammalian cells. However, excess production of ROS can induce cell death by oxidative damaging effects to intracellular biomacromolecules...
September 21, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28936553/significance-of-evaluating-tumor-infiltrating-lymphocytes-tils-and-programmed-cell-death-ligand-1-pd-l1-expression-in-breast-cancer
#7
REVIEW
Sasagu Kurozumi, Takaaki Fujii, Hiroshi Matsumoto, Kenichi Inoue, Masafumi Kurosumi, Jun Horiguchi, Hiroyuki Kuwano
The immune system affects all phases of tumor growth from initiation to progression and dissemination. Tumor-infiltrating lymphocytes (TILs) are mononuclear immune cells that infiltrate tumor tissue. Several retrospective studies have suggested the potential of TILs as a prognostic as well as predictive factor of chemotherapy in some breast cancers. On the other hand, programmed cell death protein-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) eliminate T cell activation in various types of cancers. Prospective trials to evaluate the efficacy of antibody agents to PD-1 and PD-L1 are ongoing in patients with breast cancer...
September 21, 2017: Medical Molecular Morphology
https://www.readbyqxmd.com/read/28935883/ex-vivo-expanded-human-nk-cells-survive-and-proliferate-in-humanized-mice-with-autologous-human-immune-cells
#8
Fatemeh Vahedi, Tina Nham, Sophie M Poznanski, Marianne V Chew, Mira M Shenouda, Dean Lee, Ali A Ashkar
Adoptive immune cell therapy is emerging as a promising immunotherapy for cancer. Particularly, the adoptive transfer of NK cells has garnered attention due to their natural cytotoxicity against tumor cells and safety upon adoptive transfer to patients. Although strategies exist to efficiently generate large quantities of expanded NK cells ex vivo, it remains unknown whether these expanded NK cells can persist and/or proliferate in vivo in the absence of exogenous human cytokines. Here, we have examined the adoptive transfer of ex vivo expanded human cord blood-derived NK cells into humanized mice reconstituted with autologous human cord blood immune cells...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935774/immunotherapy-a-new-and-old-approach-to-treatment-of-soft-tissue-and-bone-sarcomas
#9
REVIEW
Michael J Nathenson, Anthony P Conley, Edward Sausville
Soft tissue and bone sarcomas are a rare and heterogeneous form of cancer. With standard of care treatment options including surgery, radiation, and chemotherapy, the long-term survival is still low for high-risk soft tissue sarcoma patients. New treatment strategies are needed. Immunotherapy offers a new potential treatment paradigm with great promise. Immunotherapy of soft tissue sarcomas dates back to Dr. Coley's first use of toxins in the late 1800s. A variety of strategies of immunotherapy have been tried in soft tissue and bone sarcomas, including various vaccines and cytokines, with limited success...
September 21, 2017: Oncologist
https://www.readbyqxmd.com/read/28935151/consumption-of-garlic-and-lemon-aqueous-extracts-combination-reduces-tumor-burden-by-angiogenesis-inhibition-apoptosis-induction-and-immune-system-modulation
#10
Wamidh H Talib
OBJECTIVES: Dietary agents play an important role in cancer prevention and therapy because of their low toxicity and the perception that they are not a medicine. The aim of the present study was to investigate the anticancer effect of the administration of garlic and lemon aqueous extracts against breast cancer implanted in mice. METHODS: We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay to determine the antiproliferative effect of both extracts and their combinations...
November 2017: Nutrition
https://www.readbyqxmd.com/read/28935020/-novel-immuno-oncology-therapy-current-status-of-clinical-research-and-prospect-of-application
#11
Shijia Zhang, Shengxiang Ren
Recently, immune-oncologic therapy advanced rapidly and has been defined as another option, following surgery, radiotherapy, chemotherapy and molecular targeted therapy, for treatment of malignant diseases. To date, several immune checkpoint inhibitors and compounds have been approved to treat various of malignant diseases with efficiency. Meanwhile, more and more potential therapeutic targets in processes of the cancer immunity have been noticed. We aimed to summarize the research status and clinical prospects of novel immune-oncologic treatment agencies targeted to different steps of the cancer-immunity cycle...
September 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28935016/-clinical-development-of-immune-checkpoint-inhibitors-in-patients-with-small-cell-lung-cancer
#12
Shuang Zhang, Jingjing Liu, Ying Cheng
Small cell lung cancer (SCLC) is a poorly differentiated high-grade neuroendocrine tumor, accounts for approximately 14% of all lung cancers. SCLC is characterized by rapid growth, early metastasis without effective treatments after recurrence. It is urgently need to improve the therapy of patients with SCLC. In recent years Tumor immunotherapy has shown promising efficacy, especially in immune checkpoints including inhibitors programmed cell-death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)...
September 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28934595/copd-alters-immune-cell-composition-and-immune-checkpoint-inhibitor-efficacy-in-nsclc
#13
Nicholas M Mark, Julia Kargl, Stephanie E Busch, Grace H Y Yang, Heather E Metz, Huajia Zhang, Jesse J Hubbard, Sudhakar N J Pipavath, David K Madtes, A McGarry Houghton
RATIONALE: Chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC) are interrelated diseases with substantial mortality; the pathogenesis of both involves aberrant immune functioning. OBJECTIVE: To profile the immune cell composition and function in patients with NSCLC and describe the effect of COPD on lung and tumor microenvironments. METHODS: We profiled resected lung and tumor tissue using flow cytometry and T-cell receptor sequencing in patients with and without COPD from a prospective cohort of patients undergoing resection of NSCLC...
September 21, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28933579/innate-immune-cells-for-immunotherapy-of-autoimmune-and-cancer-disorders
#14
Carolina Schäfer, Gabriel Ascui, Carolina H Ribeiro, Mercedes López, Rafael Prados-Rosales, Pablo A González, Susan M Bueno, Claudia A Riedel, Andrés Baena, Alexis M Kalergis, Leandro J Carreño
Modulation of the immune system has been widely targeted for the treatment of several immune-related diseases, such as autoimmune disorders and cancer, due to its crucial role in these pathologies. Current available therapies focus mainly on symptomatic treatment and are often associated with undesirable secondary effects. For several years, remission of disease and subsequently recovery of immune homeostasis has been a major goal for immunotherapy. Most current immunotherapeutic strategies are aimed to inhibit or potentiate directly the adaptive immune response by modulating antibody production and B cell memory, as well as the effector potential and memory of T cells...
September 21, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28933175/-hiv-infection-a-new-disease-of-internal-medicine
#15
Svatava Snopková
Modern antiretroviral treatment belongs to the greatest success of current medicine. HIV infection has gone from a death sentence to a manageable chronic disease which develops several decades. Thanks to treatment advances, people with HIV can and do live long and full lives. In the last two decades, the incidence AIDS defining illnesses have been dramatically reduced especially opportunistic infections and malignancies, whereas the role of non-infection comorbidities has risen than age-matched HIV uninfected adults...
2017: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/28932647/immunotherapy-with-listeria-reduces-metastatic-breast-cancer-in-young-and-old-mice-through-different-mechanisms
#16
Arthee Jahangir, Dinesh Chandra, Wilber Quispe-Tintaya, Manisha Singh, Benson Chellakkan Selvanesan, Claudia Gravekamp
Cancer immunotherapy is one of the most promising and benign therapies against metastatic cancer. However, most cancer patients are old and elderly react less efficient to cancer vaccines than young adults, due to T cell unresponsiveness. Here we present data of cancer vaccination in young and old mice with metastatic breast cancer (4T1 model). We tested adaptive and innate immune responses to foreign antigens (Listeria-derived) and self-antigens (tumor-associated antigens (TAA)) and their contribution to elimination of metastases at young and old age...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932641/response-to-first-line-chemotherapy-regimen-is-associated-with-efficacy-of-nivolumab-in-non-small-cell-lung-cancer
#17
Courèche-Guillaume Kaderbhai, Corentin Richard, Jean David Fumet, Anne Aarnink, Sandra Ortiz-Cuaran, Maurice Pérol, Pascal Foucher, Bruno Coudert, Laure Favier, Aurélie Lagrange, Emeric Limagne, Romain Boidot, Sylvain Ladoire, Michel Poudenx, Marius Ilie, Paul Hofman, Pierre Saintigny, François Ghiringhelli
Nivolumab, an anti PD-1 checkpoint inhibitor has demonstrated efficacy in metastatic non-small-cell lung cancer (NSCLC) patients after failure to standard chemotherapy. Standard chemotherapy agents could promote antitumor immune response. We thus examined whether the response to first line chemotherapy could impact on nivolumab benefit. One hundred and 15 patients with NSCLC were included in this retrospective study from 4 different French centers. Forty-three squamous cell carcinomas (SCC), and 72 non-SCC received nivolumab between 2015 and 2016 (3 mg/kg IV Q2W)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932627/addition-of-anti-estrogen-therapy-to-anti-her2-dendritic-cell-vaccination-improves-regional-nodal-immune-response-and-pathologic-complete-response-rate-in-patients-with-er-pos-her2-pos-early-breast-cancer
#18
Lea Lowenfeld, Salman Zaheer, Crystal Oechsle, Megan Fracol, Jashodeep Datta, Shuwen Xu, Elizabeth Fitzpatrick, Robert E Roses, Carla S Fisher, Elizabeth S McDonald, Paul J Zhang, Angela DeMichele, Rosemarie Mick, Gary K Koski, Brian J Czerniecki
HER2-directed therapies are less effective in patients with ER(pos) compared to ER(neg) breast cancer, possibly reflecting bidirectional activation between HER2 and estrogen signaling pathways. We investigated dual blockade using anti-HER2 vaccination and anti-estrogen therapy in HER2(pos)/ER(pos) early breast cancer patients. In pre-clinical studies of HER2(pos) breast cancer cell lines, ER(pos) cells were partially resistant to CD4(+) Th1 cytokine-induced metabolic suppression compared with ER(neg) cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932226/immunomodulatory-properties-of-coriolus-versicolor-the-role-of-polysaccharopeptide
#19
REVIEW
Mohammad H Saleh, Iran Rashedi, Armand Keating
Traditional uses of herbal medicine have depended mostly on anecdotal evidence for much of history. The increasing application of scientific rigor to the study some of these traditional therapies in recent years has revealed potent bioactivity, notably demonstrated by the 2015 Nobel Prize for the discovery of an antimalarial compound from traditional Chinese herbs. Given the recent successes of immunotherapy and checkpoint blockade, there is a renewed interest in identifying new drugs with immunomodulatory effects...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28932193/safety-profile-of-anticancer-and-immune-modulating-biotech-drugs-used-in-a-real-world-setting-in-campania-region-italy-bio-cam-observational-study
#20
Cristina Scavone, Liberata Sportiello, Maria G Sullo, Carmen Ferrajolo, Rosanna Ruggiero, Maurizio Sessa, Pasquale M Berrino, Gabriella di Mauro, Liberato Berrino, Francesco Rossi, Concetta Rafaniello, Annalisa Capuano
Objectives: To investigate the occurrence of adverse events (AEs) in naïve patients receiving biotech drugs. Design: A prospective observational study. Setting: Onco-hematology, Hepato-gastroenterology, Rheumatology, Dermatology, and Neurology Units in Campania Region (Italy). Participants: 775 patients (53.81% female) with mean age 56.0 (SD 15.2). The mean follow-up/patient was 3.48 (95% confidence interval 3.13-3.84). Main outcome measures: We collected all AEs associated to biotech drugs, including serious infections and malignancies...
2017: Frontiers in Pharmacology
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