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Targeted therapy, immunotherapy

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https://www.readbyqxmd.com/read/28441264/cd19-isoforms-enabling-resistance-to-cart-19-immunotherapy-are-expressed-in-b-all-patients-at-initial-diagnosis
#1
Jeannette Fischer, Claudia Paret, Khalifa El Malki, Francesca Alt, Arthur Wingerter, Marie A Neu, Bettina Kron, Alexandra Russo, Nadine Lehmann, Lea Roth, Eva-M Fehr, Sebastian Attig, Alexander Hohberger, Thomas Kindler, Jörg Faber
B-cell acute lymphoblastic leukemia (B-ALL) is the commonest childhood cancer and the prognosis of children with relapsed or therapy refractory disease remains a challenge. Treatment with chimeric antigen receptor-modified T cells targeting the CD19 antigen (CART-19 therapy) has been presented as a promising approach toward improving the outcome of relapsed or refractory disease. However, 10%-20% of the patients suffer another relapse. Epitope-loss under therapy pressure has been suggested as a mechanism of tumor cells to escape the recognition from CART-19 therapy...
April 24, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28440434/preclinical-studies-for-the-combination-of-paclitaxel-and-curcumin-in-cancer-therapy-review
#2
Yumeng Wei, Xinlin Pu, Ling Zhao
Cancer is one of the most common causes of death and remains the first in China and the second in the US. The common treatments for cancer include surgery, radiation, chemotherapy, targeted therapy and immunotherapy, while chemotherapy remains one of the most important treatments. However, the efficacy of chemotherapy is limited due to drug induced-toxicities and resistance, particularly multiple drug resistance (MDR). Therefore, discovery and development of novel therapeutic drugs and/or combination therapy are urgently needed to reduce toxicity and improve efficacy...
April 20, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28439495/immunotherapies-in-sarcoma-updates-and-future-perspectives
#3
REVIEW
Marwan Ghosn, Elie El Rassy, Hampig Raphael Kourie
Sarcomas are malignant tumors that are characterized by a wide diversity of subtypes with various cytogenetic profiles. Despite major treatment breakthroughs, standard treatment modalities combining chemotherapy, radiotherapy, and surgery failed to improve overall survival. Therefore, high expectations are foreseen with immunotherapy upon its maturation and better understanding of its mechanism of action. This paper presents a targeted review of the published data and ongoing clinical trials in immunotherapies of sarcomas, mainly adoptive cell therapies, cancer vaccines and immune checkpoint inhibitors...
April 10, 2017: World Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28439493/targeted-therapies-in-breast-cancer-new-challenges-to-fight-against-resistance
#4
REVIEW
Viviana Masoud, Gilles Pagès
Breast cancer is the most common type of cancer found in women and today represents a significant challenge to public health. With the latest breakthroughs in molecular biology and immunotherapy, very specific targeted therapies have been tailored to the specific pathophysiology of different types of breast cancers. These recent developments have contributed to a more efficient and specific treatment protocol in breast cancer patients. However, the main challenge to be further investigated still remains the emergence of therapeutic resistance mechanisms, which develop soon after the onset of therapy and need urgent attention and further elucidation...
April 10, 2017: World Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28437678/efficacy-safety-tolerability-and-price-of-newly-approved-drugs-in-solid-tumors
#5
REVIEW
Tristan A Barnes, Eitan Amir, Arnoud J Templeton, Susana Gomez-Garcia, Beatriz Navarro, Bostjan Seruga, Alberto Ocana
BACKGROUND: New anti-cancer drugs utilize diverse mechanisms of action. Here we evaluate their differential efficacy, safety, tolerability and price. METHODS: Drugs approved for solid tumor treatment between 2000 and 2015 were identified and analyzed in subgroups: agents targeting oncogenes (group 1), anti-angiogenics (group 2), immunotherapy (group 3), and chemotherapy (group 4). Hazard ratios (HRs) were extracted from the registration trials and pooled in a meta-analysis...
April 9, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28435677/control-of-immune-cell-entry-through-the-tumour-vasculature-a-missing-link-in-optimising-melanoma-immunotherapy
#6
REVIEW
Lih Yin Tan, Carmela Martini, Zvi G Fridlender, Claudine S Bonder, Michael P Brown, Lisa M Ebert
Metastatic melanoma remains a fatal disease to many worldwide, even after the breakthrough introduction of targeted therapies such as BRAF inhibitors and immune checkpoint blockade therapies such as CTLA-4 and PD-1 inhibitors. With advances in our understanding of this disease, as well as the increasing data gathered from patient studies, the significance of the host immune response to cancer progression and response to treatment is becoming clear. More specifically, the presence of intratumoral CD8(+) cytotoxic T-cells correlates with better prognosis whereas the accumulation of monocytes/macrophages and neutrophils in the tumour is often associated with worse prognosis...
March 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28435391/programmed-cell-death-1-checkpoint-inhibitors-in-the-treatment-of-patients-with-advanced-melanoma
#7
REVIEW
Jacek Mackiewicz, Andrzej Mackiewicz
The treatment landscape of advanced melanoma has changed significantly following the discovery and marketing authorisation of immune checkpoints inhibitors. Ipilimumab (anti-CTLA-4) was the first one to be approved, and it. demonstrated long-term survival in about 20% of patients. Subsequently, anti-programmed cell death-1 (a-PD-1) antibodies (pembrolizuamb, nivolumab), inhibitors of PD-1/programmed cell death-1 ligand (PD1-L) synapse, showed higher clinical efficacy with lower toxicity comparing to ipilimumab...
2017: Contemporary Oncology Współczesna Onkologia
https://www.readbyqxmd.com/read/28434399/the-next-generation-of-immunotherapy-keeping-lung-cancer-in-check
#8
REVIEW
Ashwin Somasundaram, Timothy F Burns
Lung cancer is the deadliest malignancy with more cancer deaths per year than the next three cancers combined. Despite remarkable advances in targeted therapy, advanced lung cancer patients have not experienced a significant improvement in mortality. Lung cancer has been shown to be immunogenic and responsive to checkpoint blockade therapy. Checkpoint signals such as CTLA-4 and PD-1/PD-L1 dampen T cell activation and allow tumors to escape the adaptive immune response. Response rates in patients with pretreated, advanced NSCLC were much higher and more durable with PD-1 blockade therapy compared to standard-of-care, cytotoxic chemotherapy...
April 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28434255/daratumumab-for-the-treatment-of-multiple-myeloma
#9
Cyrille Touzeau, Philippe Moreau
Proteasome inhibitors and immunomodulatory drugs have contributed to the dramatic improvement in survival for patients with myeloma over the past decades. However, the disease typically relapses and new classes of drugs are needed. In 2015, two monoclonal antibodies were approved for the treatment of patients with relapsed multiple myeloma, and immunotherapy has rapidly become indispensable in the management of myeloma patients. Areas covered: Here, the authors discuss the published data regarding the mechanism of action, safety and clinical efficacy of the CD38-targeted monoclonal antibody daratumumab for the treatment of patients with multiple myeloma...
April 24, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28434148/advancing-chimeric-antigen-receptor-t-cell-therapy-with-crispr-cas9
#10
REVIEW
Jiangtao Ren, Yangbing Zhao
The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (CRISPR/Cas9) system, an RNA-guided DNA targeting technology, is triggering a revolution in the field of biology. CRISPR/Cas9 has demonstrated great potential for genetic manipulation. In this review, we discuss the current development of CRISPR/Cas9 technologies for therapeutic applications, especially chimeric antigen receptor (CAR) T cell-based adoptive immunotherapy. Different methods used to facilitate efficient CRISPR delivery and gene editing in T cells are compared...
April 22, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28432037/investigating-in-vitro-and-in-vivo-%C3%AE-v%C3%AE-6-integrin-receptor-targeting-liposomal-alendronate-for-combinatory-%C3%AE-%C3%AE-t-cell-immunotherapy
#11
Naomi O Hodgins, Wafa' T Al-Jamal, Julie T-W Wang, Rebecca Klippstein, Jane K Sosabowski, John F Marshall, John Maher, Khuloud T Al-Jamal
The αvβ6 integrin receptor has been shown to be overexpressed on many types of cancer cells, resulting in a more pro-invasive and aggressive phenotype, this makes it an attractive target for selective drug delivery. In tumours that over-express the αvβ6 receptor, cellular uptake of liposomes can be enhanced using ligand-targeted liposomes. It has previously been shown in both in vitro and in vivo studies that liposomal alendronate (L-ALD) can sensitise cancer cells to destruction by Vγ9Vδ2 T cells. It is hypothesised that by using the αvβ6-specific peptide A20FMDV2 as a targeting moiety for L-ALD, the therapeutic efficacy of this therapy can be increased in αvβ6 positive tumours...
April 18, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28431262/immunologic-approaches-for-the-treatment-of-multiple-myeloma
#12
REVIEW
Leo Rasche, Niels Weinhold, Gareth J Morgan, Frits van Rhee, Faith E Davies
The FDA approval of two monoclonal antibodies in 2015has heralded a new era of targeted immunotherapies for multiple myeloma (MM). In this review we discuss the recent approaches using different immunological components to treat MM. In particular, we review current monoclonal antibody based therapies, engineered T- and NK cell products, 'off-target' immunomodulation, and strategies utilizing allogeneic cell transplantation in MM. We discuss how an immunologic approach offers promise for the treatment of this genetically heterogeneous disease, and how patients with acquired drug resistance may particularly benefit from these therapies...
April 6, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28430580/expression-status-of-folate-receptor-alpha-is-a-predictor-of-survival-in-pancreatic-ductal-adenocarcinoma
#13
Lei Cai, Theodoros Michelakos, Cristina R Ferrone, Liyuan Zhang, Vikram Deshpande, Qi Shen, Albert De Leo, Teppei Yamada, Gong Zhang, Soldano Ferrone, Xinhui Wang
Pancreatic ductal adenocarcinoma (PDAC) has one of the poorest prognosis among malignancies. Thus, the identification of markers useful in developing innovative diagnostic and therapeutic methods is an imperative need. Folate receptor alpha (FRα) has been associated with prognosis in several cancers and has served as a target of novel anti-tumor therapies. However, FRα expression in PDAC and its correlation with the clinical course of the disease has not been thoroughly investigated. In this study, we analyzed FRα expression in 140 PDAC specimens and 7 PDAC cell lines in order to define the significance of FRα expression in PDAC and its potential role as a target for immunotherapy...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429069/mupexi-prediction-of-neo-epitopes-from-tumor-sequencing-data
#14
Anne-Mette Bjerregaard, Morten Nielsen, Sine Reker Hadrup, Zoltan Szallasi, Aron Charles Eklund
Personalization of immunotherapies such as cancer vaccines and adoptive T cell therapy depends on identification of patient-specific neo-epitopes that can be specifically targeted. MuPeXI, the mutant peptide extractor and informer, is a program to identify tumor-specific peptides and assess their potential to be neo-epitopes. The program input is a file with somatic mutation calls, a list of HLA types, and optionally a gene expression profile. The output is a table with all tumor-specific peptides derived from nucleotide substitutions, insertions, and deletions, along with comprehensive annotation, including HLA binding and similarity to normal peptides...
April 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28428886/vaccination-with-inhibin-%C3%AE-provides-effective-immunotherapy-against-testicular-stromal-cell-tumors
#15
Robert Aguilar, Justin M Johnson, Patrick Barrett, Vincent K Tuohy
BACKGROUND: Testicular cancer is the most common male neoplasm occurring in men between the ages of 20 and 34. Although germ-line testicular tumors respond favorably to current standard of care, testicular stromal cell (TSC) tumors derived from Sertoli cells or Leydig cells often fail to respond to chemotherapy or radiation therapy and have a 5-year overall survival significantly lower than the more common and more treatable germ line testicular tumors. METHODS: To improve outcomes for TSC cancer, we have developed a therapeutic vaccine targeting inhibin-α, a protein produced by normal Sertoli and Leydig cells of the testes and expressed in the majority of TSC tumors...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28428882/differential-phenotypes-of-memory-cd4-and-cd8-t-cells-in-the-spleen-and-peripheral-tissues-following-immunostimulatory-therapy
#16
Gail D Sckisel, Annie Mirsoian, Christine M Minnar, Marka Crittenden, Brendan Curti, Jane Q Chen, Bruce R Blazar, Alexander D Borowsky, Arta M Monjazeb, William J Murphy
BACKGROUND: Studies assessing immune parameters typically utilize human PBMCs or murine splenocytes to generate data that is interpreted as representative of immune status. Using splenocytes, we have shown memory CD4-T cells that expand following systemic immunostimulatory therapies undergo rapid IFNg-mediated activation induced cell death (AICD) resulting in a net loss of total CD4-T cells which correlates with elevated PD-1 expression. This is in contrast to CD8-T cells which expand with minimal PD-1 upregulation and apoptosis...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28428017/outcomes-and-toxicity-following-high-dose-radiation-therapy-in-15-fractions-for-non-small-cell-lung-cancer
#17
Penny Fang, Cameron W Swanick, Todd A Pezzi, Zhongxing Liao, James Welsh, Steven H Lin, Daniel R Gomez
PURPOSE: Accelerated hypofractionated radiation therapy (AHRT) is increasingly used for select lung cancer patients. We evaluated clinical outcomes and predictors of pulmonary/esophageal toxicity in patients treated with ≥52.5 Gy in 15 fractions. METHODS AND MATERIALS: We evaluated 229 patients treated with radiation therapy doses ≥52.5 Gy in 15 fractions for non-small cell lung cancer from January 2009 through January 2016. Toxicity was scored using Common Terminology Criteria for Adverse Events, v4...
March 9, 2017: Practical Radiation Oncology
https://www.readbyqxmd.com/read/28427519/a-comprehensive-review-of-immunotherapies-in-prostate-cancer
#18
REVIEW
Manuel Caitano Maia, Aaron R Hansen
Prostate cancer is the second most common malignant neoplasm in men worldwide and the fifth cause of cancer-related death. Although multiple new agents have been approved for metastatic castration resistant prostate cancer over the last decade, it is still an incurable disease. New strategies to improve cancer control are needed and agents targeting the immune system have shown encouraging results in many tumor types. Despite being attractive for immunotherapies due to the expression of various tumor associated antigens, the microenvironment in prostate cancer is relatively immunosuppressive and may be responsible for the failures of various agents targeting the immune system in this disease...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28427157/the-anti-tumor-efficacy-of-3c23k-a-glyco-engineered-humanized-anti-misrii-antibody-in-an-ovarian-cancer-model-is-mainly-mediated-by-engagement-of-immune-effector-cells
#19
Pauline Estupina, Alexandre Fontayne, Jean-Marc Barret, Nathalie Kersual, Olivier Dubreuil, Marion Le Blay, Alexandre Pichard, Marta Jarlier, Martine Pugnière, Maëva Chauvin, Thierry Chardès, Jean-Pierre Pouget, Emmanuel Deshayes, Alexis Rossignol, Toufik Abache, Christophe de Romeuf, Aurélie Terrier, Lucie Verhaeghe, Christine Gaucher, Jean-François Prost, André Pèlegrin, Isabelle Navarro-Teulon
Ovarian cancer is the leading cause of death in women with gynecological cancers and despite recent advances, new and more efficient therapies are crucially needed. Müllerian Inhibiting Substance type II Receptor (MISRII, also named AMHRII) is expressed in most ovarian cancer subtypes and is a novel potential target for ovarian cancer immunotherapy. We previously developed and tested 12G4, the first murine monoclonal antibody (MAb) against human MISRII. Here, we report the humanization, affinity maturation and glyco-engineering steps of 12G4 to generate the Fc-optimized 3C23K MAb, and the evaluation of its in vivo anti-tumor activity...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426952/plant-viruses-and-bacteriophages-for-delivery-in-medicine-and-biotechnology
#20
REVIEW
Anna E Czapar, Nicole F Steinmetz
There are a wide variety of synthetic and naturally occurring nanomaterials under development for nanoscale cargo-delivery applications. Viruses play a special role in these developments, because they can be regarded as naturally occurring nanomaterials evolved to package and deliver cargos. While any nanomaterial has its advantage and disadvantages, viral nanoparticles (VNPs), in particular the ones derived from plant viruses and bacteriophages, are attractive options for cargo-delivery as they are biocompatible, biodegradable, and non-infectious to mammals...
April 17, 2017: Current Opinion in Chemical Biology
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