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Combined immunotherapy

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https://www.readbyqxmd.com/read/29223828/rationale-for-combination-of-therapeutic-antibodies-targeting-tumor-cells-and-immune-checkpoint-receptors-harnessing-innate-and-adaptive-immunity-through-igg1-isotype-immune-effector-stimulation
#1
REVIEW
Robert L Ferris, Heinz-Josef Lenz, Anna Maria Trotta, Jesús García-Foncillas, Jeltje Schulten, François Audhuy, Marco Merlano, Gerard Milano
Immunoglobulin (Ig) G1 antibodies stimulate antibody-dependent cell-mediated cytotoxicity (ADCC). Cetuximab, an IgG1 isotype monoclonal antibody, is a standard-of-care treatment for locally advanced and recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) and metastatic colorectal cancer (CRC). Here we review evidence regarding the clinical relevance of cetuximab-mediated ADCC and other immune functions and provide a biological rationale concerning why this property positions cetuximab as an ideal partner for immune checkpoint inhibitors (ICIs) and other emerging immunotherapies...
December 2, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29222400/nkg2d-based-car-t-cells-and-radiotherapy-exert-synergistic-efficacy-in-glioblastoma
#2
Tobias Weiss, Michael Weller, Matthias Guckenberger, Charles L Sentman, Patrick Roth
Chimeric antigen receptor (CAR) T cell therapy is an emerging immunotherapy against several malignancies including glioblastoma, the most common and most aggressive malignant primary brain tumor in adults. The challenges in solid tumor immunotherapy comprise heterogenously expressed tumor target antigens and restricted trafficking of CAR T cells to and impaired long-term persistence at the tumor site, as well as the unaddressed integration of CAR T cell therapy into conventional anti-cancer treatments. We addressed these questions using a NKG2D-based chimeric antigen receptor construct (chNKG2D) in fully immunocompetent orthotopic glioblastoma mouse models...
December 8, 2017: Cancer Research
https://www.readbyqxmd.com/read/29222257/is-molecular-remission-the-goal-of-multiple-myeloma-therapy
#3
REVIEW
Faith E Davies
The increased number of effective therapies and the wider use of combinations that give deeper remissions have resulted in a reassessment of the goals of myeloma therapy. With the advent of new therapeutic strategies and diagnostic tools, achievement of minimal residual disease (MRD)-negative status has become increasingly important, with some even considering it as the primary endpoint for therapy. The level of MRD that is aimed for is a continuous, rather than an absolute variable, with studies in both transplant-eligible and -noneligible patients showing that the level of MRD achieved is predictive of progression-free survival and overall survival, with an improvement in survival of approximately 1 year for each log-depletion in MRD level...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222234/progress-in-adult-all-incorporation-of-new-agents-to-frontline-treatment
#4
REVIEW
Jessica Leonard, Wendy Stock
Treatment of acute lymphoblastic leukemia (ALL) in adults remains a challenge, as the delivery of intensive chemotherapeutic regimens in this population is less feasible than it is in the pediatric population. This has led to higher rates of treatment-related toxicity as well as lower overall survival in the adult population. Over the past several years, a host of novel therapies (eg, immunotherapy and targeted therapies) with better tolerability than traditional chemotherapy are now being introduced into the relapsed/refractory population with very encouraging results...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29221713/effect-of-grass-sublingual-tablet-immunotherapy-is-similar-in-children-and-adults-a-bayesian-approach-to-design-pediatric-sublingual-immunotherapy-trials
#5
Amarjot Kaur, David Skoner, Joseph Ibrahim, Qing Li, Richard F Lockey, Michael Blaiss, Albrecht Bufe, Jens Strodl Andersen, Giorgio Walter Canonica, Hendrik Nolte
BACKGROUND: Large sample sizes are needed for sublingual immunotherapy (SLIT) trials due to inherent data variability secondary to inconsistent allergen exposure. Obtaining large sample sizes for pediatric SLIT trials is challenging, but a Bayesian approach using prior adult data can reduce the necessary sample size. OBJECTIVE: To describe how a Bayesian framework utilizing prior information from adult trials can be used to improve pediatric SLIT clinical development...
December 5, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29220291/emerging-targeted-and-immune-based-therapies-in-sarcoma
#6
Seth M Pollack, Matthew Ingham, Matthew B Spraker, Gary K Schwartz
Soft tissue and bone sarcomas are malignancies of mesenchymal origin, and more than 50 subtypes are defined. For most sarcomas, locally advanced or unresectable disease is still treated with cytotoxic chemotherapy. Recently, our understanding of subtype-specific cancer biology has expanded, and it has revealed distinct molecular alterations responsible for tumor initiation and progression. These findings have motivated the development of targeted therapies that are being evaluated in subtype-specific or biomarker-driven clinical trials...
December 8, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29220290/synovial-sarcoma-current-concepts-and-future-perspectives
#7
Silvia Stacchiotti, Brian Andrew Van Tine
Synovial sarcoma (SS) is a rare sarcoma driven by a translocation between SS18 and SSX 1, 2, or 4. With approximately 800 to 1,000 cases a year in the United States, it most commonly affects young adults between the ages of 15 and 30 years. The resultant tumors are either monophasic (pure sarcomas), biphasic (a combination or epithelioid and sarcomatous components), or poorly differentiated. The hybrid transcription factor SS18:SSX alters SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling and global methylation patterns that may allow for future therapeutic opportunities...
December 8, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29217527/merkel-cell-carcinoma-in-the-age-of-immunotherapy-facts-and%C3%A2-hopes
#8
Aric Colunga, Thomas Pulliam, Paul Nghiem
Merkel cell carcinoma (MCC) is a rare (~2,000 US cases/year) but aggressive neuroendocrine tumor of the skin. For advanced MCC, cytotoxic chemotherapy only infrequently (<10% of cases) offers durable clinical responses (>1 year) suggesting a great need for improved therapeutic options. In 2008, the Merkel cell polyomavirus (MCPyV) was discovered and is clonally integrated in ~80% of MCC tumors. The remaining 20% of MCC tumors have large numbers of UV-associated mutations. Importantly, both the UV-induced-neoantigens in virus-negative tumors and the MCPyV T antigen oncogenes that are required for virus-positive tumor growth are immunogenic...
December 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29217301/-gut-microbiota-what-impact-on-colorectal-carcinogenesis-and-treatment
#9
REVIEW
Antoine Bruneau, Minh-Tam Baylatry, Anne Christine Joly, Harry Sokol
The gut microbiota, composed of 1014 microorganisms, is now considered as a "hidden organ", regarding to its digestive, metabolic and immune functions, which are helpful to its host. For the last 15 years, advances in molecular biology have highlighted the association of gut microbiota dysbiosis with several diseases, including colorectal cancer. An increased abundance of some bacteria (including Fusobacterium nucleatum, Bacteroides fragilis, Escherichia coli) is associated with cancer, whereas others seem to be protective (Faecalibacterium prausnitzii)...
December 4, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/29214012/evidence-of-the-efficacy-and-safety-of-house-dust-mite-subcutaneous-immunotherapy-in-elderly-allergic-rhinitis-patients-a-randomized-double-blind-placebo-controlled-trial
#10
Andrzej Bożek, Krzysztof Kołodziejczyk, Renata Kozłowska, Giorgio Walter Canonica
Background: Allergen specific immunotherapy (AIT) in elderly patients is controversial, and there is still little evidence supporting the safety and efficacy of this treatment in this population. The study objective was to evaluate the safety and efficacy of AIT for house dust mite allergens in patients over 65 years of age with allergic rhinitis (AR) and a documented allergy to house dust mites. The primary endpoint was the change from baseline in the mean average adjusted symptom score (AAdSS) and the total combined rhinitis score (TCRS) difference in the least square means for the label compared to placebo...
2017: Clinical and Translational Allergy
https://www.readbyqxmd.com/read/29213216/tumor-infiltrating-cd4-t-cells-in-patients-with-gastric-cancer
#11
Long Yuan, Benling Xu, Peng Yuan, Jinxue Zhou, Peng Qin, Lu Han, Guangyu Chen, Zhenlei Wang, Zengci Run, Peng Zhao, Quanli Gao
Background: T lymphocytes play an indispensably important role in clearing virus and tumor antigen. There is little knowledge about impacts of inhibitory molecules with cytokine on tumor-infiltrating CD4+ T-cells in the presence of gastric cancer (GC). This study investigated the distribution of tumor-infiltrating T-cells subset and the differentiation as well as inhibitory phenotype of T-cells from blood and tissues of GC patients. Materials and methods: Patients with GC diagnosed on the basis of pre-operative staging and laparotomy findings were approached for enrollment between 2014 and 2015 at the Affiliated Cancer Hospital of Zhengzhou University, China...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/29213157/immunotherapy-and-gene-therapy-as-novel-treatments-for-cancer
#12
REVIEW
Martha Montserrat Rangel-Sosa, Estuardo Aguilar-Córdova, Augusto Rojas-Martínez
The immune system interacts closely with tumors during the disease development and progression to metastasis. The complex communication between the immune system and the tumor cells can prevent or promote tumor growth. New therapeutic approaches harnessing protective immunological mechanisms have recently shown very promising results. This is performed by blocking inhibitory signals or by activating immunological effector cells directly. Immune checkpoint blockade with monoclonal antibodies directed against the inhibitory immune receptors CTLA-4 and PD-1 has emerged as a successful treatment approach for patients with advanced melanoma...
September 30, 2017: Colombia Médica: CM
https://www.readbyqxmd.com/read/29213052/exosomes-from-antigen-pulsed-dendritic-cells-induce-stronger-antigen-specific-immune-responses-than-microvesicles-in-vivo
#13
Casper J E Wahlund, Gözde Güclüler, Stefanie Hiltbrunner, Rosanne E Veerman, Tanja I Näslund, Susanne Gabrielsson
Extracellular vesicles (EV), including exosomes and microvesicles (MV), represent a rapidly expanding field of research with diagnostic and therapeutic applications. Although many aspects of EV function remain to be revealed and broad investigations are warranted, most published findings focus on only one vesicle category or a non-separated mix of EVs. In this paper, we investigated both MVs and exosomes from Ovalbumin (OVA)-pulsed dendritic cells for their immunostimulatory potential side-by-side in vivo. Only exosomes induced antigen-specific CD8+ T-cells, and were more efficient than MVs in eliciting antigen-specific IgG production...
December 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29210217/i131-reinforces-antitumor-activity-of-metuximab-by-reversing-epithelial-mesenchymal-transition-via-vegfr-2-signaling-in-hepatocellular-carcinoma
#14
Lu Wu, Bin Sun, Xuejing Lin, Chunying Liu, Haihua Qian, Lei Chen, Yefa Yang, Feng Shen, Changqing Su
CD147 is highly expressed in hepatocellular carcinoma (HCC) and associated with the invasion and metastasis of HCC. The efficacy of I131 -metuximab (I131 -mab), a newly developed agent that targets CD147, as a radio-immunotherapy for local HCC, has been validated in clinical practice. However, the synergistic anticancer activity and molecular mechanism of different conjugated components within I131 -mab remain unclear. In this study, the cytological experiments proved that I131 -mab inhibited the proliferation and invasion of HCC cells...
December 6, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/29209558/development-and-clinical-application-of-anti-her2-monoclonal-and-bispecific-antibodies-for-cancer-treatment
#15
REVIEW
Shengnan Yu, Qian Liu, Xinwei Han, Shuang Qin, Weiheng Zhao, Anping Li, Kongming Wu
HER2-targeted immunotherapy consists of monoclonal antibodies (e.g. trastuzumab, pertuzumab), bispecific antibodies (e.g. MM-111, ertumaxomab) and activated T cells armed with anti-HER2 bispecific antibody (HER2Bi-aATC). Trastuzumab is a classic drug for the treatment of HER2 positive metastatic breast cancer. The combined application of pertuzumab, trastuzumab and paclitaxel has been suggested as a standard therapy for HER2 positive advanced breast cancer. The resistance to anti-HER2 antibody has resulted in disease progression...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29209232/the-clinicopathological-and-prognostic-implications-of-foxp3-regulatory-t-cells-in-patients-with-colorectal-cancer-a-meta-analysis
#16
Peipei Xu, Wei Fan, Zheng Zhang, June Wang, Ping Wang, Yirong Li, Mingxia Yu
Background and Objective: Forkhead box P3 (FoxP3) is known as the specific marker for regulatory T lymphocytes (Tregs), which are responsible for self-tolerance and disturb the antitumor immunity. However, the prognostic implication of tumor-infiltrating FoxP3+ Tregs in patients with colorectal cancer (CRC) still remains controversial. The aim of this present study was to investigate the prognostic role of FoxP3+ Tregs in CRC through meta-analysis. Methods: PubMed, Embase and Web of Science were searched for relevant articles up to December 12, 2016...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29207115/current-status-and-future-prospects-of-the-strategy-of-combining-car%C3%A2-t-with-pd%C3%A2-1-blockade-for-antitumor-therapy-review
#17
Jinjing Xu, Qing Zhang, Kang Tian, Haiyu Wang, Hong Yin, Junnian Zheng
The immune system serves an important role in controlling and eradicating malignant cells. Immunotherapy for treating tumors has received much attention in recent years due to its marked effect. There are two approaches which currently lead this field: Chimeric antigen receptor‑modified T‑cell immunotherapy (CAR‑T) and programmed cell death protein-1 blockade (PD‑1 blockade). CAR‑T has emerged as a promising regimen for the treatment of a range of types of cancer, including chronic lymphoid leukemia and neuroblastoma, with studies of long term remission in certain patients...
November 22, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29205200/immunotherapy-in-metastatic-urothelial-carcinoma-focus-on-immune-checkpoint-inhibition
#18
REVIEW
Arlene Siefker-Radtke, Brendan Curti
Immunotherapy has been used in localized urothelial carcinoma for decades, especially in the treatment of superficial disease, in which instillation of BCG is a commonly used treatment option. Clinical investigations based on new insights into the immunogenic potential of metastatic urothelial carcinoma have led to the accelerated FDA approval of the immune checkpoint inhibitors atezolizumab, nivolumab, durvalumab, avelumab, and pembrolizumab. Preliminary findings suggest additional benefits of combinations of immunotherapeutic agents as a future treatment approach in metastatic urothelial carcinoma...
December 5, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/29204524/distant-intracranial-failure-in-melanoma-brain-metastases-treated-with-stereotactic-radiosurgery-in-the-era-of-immunotherapy-and-targeted-agents
#19
Sahaja Acharya, Mustafaa Mahmood, Daniel Mullen, Deshan Yang, Christina I Tsien, Jiayi Huang, Stephanie M Perkins, Keith Rich, Michael Chicoine, Eric Leuthardt, Joshua Dowling, Gavin Dunn, Jesse Keller, Clifford G Robinson, Christopher Abraham
Purpose: Stereotactic radiosurgery (SRS) in combination with immunotherapy (IMT) or targeted therapy is increasingly being used in the setting of melanoma brain metastases (MBMs). The synergistic properties of combination therapy are not well understood. We compared the distant intracranial failure rates of intact MBMs treated with SRS, SRS + IMT, and SRS + targeted therapy. Methods and materials: Combination therapy was defined as delivery of SRS within 3 months of IMT (anti-CTLA-4 /anti-PD-1 therapy) or targeted therapy (BRAF/MEK inhibitors)...
October 2017: Advances in Radiation Oncology
https://www.readbyqxmd.com/read/29204520/comprehensive-assessment-of-circulating-immune-cell-populations-in-response-to-stereotactic-body-radiation-therapy-in-patients-with-liver-cancer
#20
Michael P Gustafson, Svetlana Bornschlegl, Sean S Park, Dennis A Gastineau, Lewis R Roberts, Allan B Dietz, Christopher L Hallemeier
Stereotactic body radiation therapy (SBRT) can positively influence an antitumor immune response by inducing necrotic cell death. SBRT also been shown to eliminate tumors outside the radiation therapy field through an immune-mediated process known as the abscopal effect. Recent advances in immunotherapy may provide new therapeutic approaches for patients with liver cancer. Therefore, understanding the immune status of patients with cancer will likely guide how immunotherapy might be used in combination with SBRT...
October 2017: Advances in Radiation Oncology
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