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https://www.readbyqxmd.com/read/28926977/mouse-monoclonal-antibodies-generated-from-full-length-human-cereblon-detection-of-cereblon-protein-in-patients-with-multiple-myeloma
#1
Xiubao Chang, Qinqin Xu, Yuexian Hou, Cynthia Li, Ye Xu, A Keith Stewart
Immunomodulatory drugs (IMiDs) are profoundly active compounds in the treatment of patients with multiple myeloma (MM). However, despite the fact that treatment with IMiDs has dramatically improved survival for patients with MM, the majority of MM patients develop IMiDs resistance over time. We have found that expression of functional cereblon is required for IMiDs' action. In addition, it has been reported that cells expressing high levels of cereblon are resistant to proteasome inhibitor, implying that patients with high levels of cereblon should be resistant to proteasome inhibitor...
September 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28926943/monoclonal-antibodies-in-preclinical-eae-models-of-multiple-sclerosis-a-systematic-review
#2
REVIEW
Katja Schmitz, Gerd Geisslinger, Irmgard Tegeder
Monoclonal antibodies (mAb) are promising therapeutics in multiple sclerosis and multiple new candidates have been developed, hence increasing the need for some agreement for preclinical mAb studies. We systematically analyzed publications of experimental autoimmune encephalomyelitis (EAE) studies showing effects of monoclonal antibodies. A PubMed search retrieved 570 records, out of which 122 studies with 253 experiments were eligible based on experimental design, number of animals and presentation of time courses of EAE scores...
September 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28926521/blockade-of-hla-antibody-triggered-classical-complement-activation-in-sera-from-subjects-dosed-with-the-anti-c1s-monoclonal-antibody-tnt009-results-from-a-randomized-first-in-human-phase-1-trial
#3
Jakob Mühlbacher, Bernd Jilma, Markus Wahrmann, Johann Bartko, Farsad Eskandary, Christian Schörgenhofer, Michael Schwameis, Graham C Parry, James C Gilbert, Sandip Panicker, Georg A Böhmig
BACKGROUND: Complement may play a key role in antibody-mediated rejection. A promising therapeutic approach may be classical pathway (CP) inhibition at the level of early component C1. METHODS: In this first-in-human, double-blind, randomized placebo-controlled phase 1 trial, we evaluated the safety and complement inhibitory effect of TNT009, a humanized monoclonal anti-C1s antibody. Sixty-four adult healthy volunteers received either single (n = 48; 7 consecutive cohorts, 0...
October 2017: Transplantation
https://www.readbyqxmd.com/read/28926365/primary-cutaneous-diffuse-large-b-cell-lymphoma-leg-type-with-spontaneous-regression-after-biopsy
#4
Gabriel Marrero-Alemán, Társila Montenegro-Dámaso, Yeray Peñate
Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) represents approximately 20% of cutaneous B lymphomas with an intermediate prognosis. Spontaneous regression is uncommon; there are only 2 published cases. An 83-year-old woman presented 2 orange erythematous nodules on the back of her right leg with an elastic consistency, infiltrated, painful to the touch, and of an 8-month evolution. A histological examination revealed a dense cellular dermo-hypodermic infiltrate sparing the papillary dermis, composed of large cells with immunoblast and centroblast morphology and frequent mitosis...
October 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28926356/development-of-bell-s-palsy-after-treatment-with-ipilimumab-and-nivolumab-for-metastatic-melanoma-a-case-report
#5
Julia M Zecchini, Sara Kim, Kendra Yum, Philip Friedlander
Ipilimumab is a human monoclonal antibody that targets cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), and it is FDA approved for the treatment of unresectable or metastatic melanoma. Immune-related adverse events (irAEs) of gastrointestinal, dermatologic, and endocrine origin are commonly seen, ranging between 18% and 44%, with immune checkpoint inhibitors (anti-CTLA-4 and anti-PD-1/PD-L1). Rare irAEs include neurological, renal, and hematologic toxicities. Bell's palsy is a form of neurological toxicity that presents as an idiopathic paralysis of the muscles on one side of the face...
September 18, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28925793/sequential-administration-of-mva-based-vaccines-and-pd-1-pd-l1-blocking-antibodies-confers-measurable-benefits-on-tumor-growth-and-survival-preclinical-studies-with-mva-%C3%AE-gal-and-mva-muc1-tg4010-in-a-murine-tumor-model
#6
Christelle Remy-Ziller, Christine Thioudellet, Julie Hortelano, Murielle Gantzer, Virginie Nourtier, Marie-Christine Claudepierre, Benoit Sansas, Xavier Préville, Kaïdre Bendjama, Eric Quemeneur, Karola Rittner
TG4010, a Modified Vaccinia virus Ankara (MVA) expressing human mucin1 (MUC1) has demonstrated clinical benefit for patients suffering from advanced non-small cell lung cancer (NSCLC) in combination with chemotherapy. To support its development, preclinical experiments were performed with either TG4010 or β-galactosidase-encoding MVA vector (MVA-βgal) in mice presenting tumors in the lung. Tumor growth was obtained after intravenous injection of CT26 murine colon cancer cells, engineered to express either MUC1 or βgal...
September 19, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28924167/a-toxic-conformer-of-a%C3%AE-42-with-a-turn-at-22-23-is-a-novel-therapeutic-target-for-alzheimer-s-disease
#7
Naotaka Izuo, Chihiro Kasahara, Kazuma Murakami, Toshiaki Kume, Masahiro Maeda, Kazuhiro Irie, Koutaro Yokote, Takahiko Shimizu
Immunotherapy targeting Aβ42 is drawing attention as a possible therapeutic approach for Alzheimer's disease (AD). Considering the significance of reported oligomerized Aβ42 species, selective targeting of the oligomer will increase the therapeutic efficacy. However, what kinds of oligomers are suitable targets for immunotherapy remains unclear. We previously identified a toxic conformer of Aβ42, which has a turn structure at 22-23 ("toxic turn"), among Aβ42 conformations. This toxic conformer of Aβ42 has been reported to show rapid oligomerization and to exhibit strong neurotoxicity and synaptotoxicity...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28923838/syngeneic-mouse-models-of-oral-cancer-are-effectively-targeted-by-anti-cd44-based-nir-pit
#8
Tadanobu Nagaya, Yuko Nakamura, Shuhei Okuyama, Fusa Ogata, Yasuhiro Maruoka, Peter L Choyke, Clint Alen, Hisataka Kobayashi
Oral cavity squamous cell carcinoma (OSCC) is considered one of the most aggressive subtypes of cancer. Anti-CD44 monoclonal antibodies (mAbs) are a potential therapy against CD44 expressing OSCC, however, to date the therapeutic effects have been disappointing. Here, a new cancer treatment is described, near-infrared photoimmunotherapy (NIR-PIT), that uses anti-CD44 mAbs conjugated to the photoabsorber, IR700DX. This conjugate is injected into mice harboring one of three CD44 expressing syngeneic murine oral cancer cell (MOC) lines, MOC1 (immunogenic), MOC2 mKate2 (moderately immunogenic), and MOC2-luc (poorly immunogenic)...
September 18, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28923100/checkpoint-inhibitor-is-active-against-large-cell-neuroendocrine-carcinoma-with-high-tumor-mutation-burden
#9
Victoria E Wang, Anatoly Urisman, Lee Albacker, Siraj Ali, Vincent Miller, Rahul Aggarwal, David Jablons
BACKGROUND: Large cell neuroendocrine tumor (LCNEC) of the lung is a rare and aggressive tumor similar to small cell lung cancer (SCLC). Thus, it is often treated similarly to SCLC in the front-line setting with a platinum doublet. However, treatment for patients beyond the first line remains undefined. CASE PRESENTATION: We report the case of a patient with stage IB LCNEC (PD-L1 negative but positive for PD-L1 amplification and tumor mutation burden high) who progressed after adjuvant chemotherapy after surgery and subsequent therapy with an antibody drug conjugate targeting a neuroendocrine-specific cell surface marker but achieved a significant and durable response with pembrolizumab, a humanized IgG4 monoclonal anti-PD-1 antibody...
September 19, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28921867/polymer-cancerostatics-targeted-with-an-antibody-fragment-bound-via-a-coiled-coil-motif-in-vivo-therapeutic-efficacy-against-murine-bcl1-leukemia
#10
Michal Pechar, Robert Pola, Olga Janoušková, Irena Sieglová, Vlastimil Král, Milan Fábry, Barbora Tomalová, Marek Kovář
A BCL1 leukemia-cell-targeted polymer-drug conjugate with a narrow molecular weight distribution consisting of an N-(2-hydroxypropyl)methacrylamide copolymer carrier and the anticancer drug pirarubicin is prepared by controlled radical copolymerization followed by metal-free click chemistry. A targeting recombinant single chain antibody fragment (scFv) derived from a B1 monoclonal antibody is attached noncovalently to the polymer carrier via a coiled coil interaction between two complementary peptides. Two pairs of coiled coil forming peptides (abbreviated KEK/EKE and KSK/ESE) are used as linkers between the polymer-pirarubicin conjugate and the targeting protein...
September 15, 2017: Macromolecular Bioscience
https://www.readbyqxmd.com/read/28921650/antibody-drug-conjugates-as-cancer-therapeutics-past-present-and-future
#11
Heather E Vezina, Monette Cotreau, Tae H Han, Manish Gupta
Antibody-drug conjugates (ADCs) represent an innovative therapeutic approach that provides novel treatment options and hope for patients with cancer. By coupling monoclonal antibodies (mAbs) to cytotoxic small-molecule payloads with a plasma-stable linker, ADCs offer the potential for increased drug specificity and fewer off-target effects than systemic chemotherapy. As evidence for the potential of these therapies, many new ADCs are in various stages of clinical development. Because their structure poses unique challenges to pharmacokinetic and pharmacodynamic characterization, it is critical to recognize the differences between ADCs and conventional chemotherapy in the design of ADC clinical development strategies...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28921644/clinical-pharmacology-considerations-for-the-development-of-immune-checkpoint-inhibitors
#12
Jennifer Sheng, Shivani Srivastava, Kinjal Sanghavi, Zheng Lu, Brian J Schmidt, Akintunde Bello, Manish Gupta
Immuno-oncology works through activation of the patient's immune system against cancer, with several advantages over other treatment approaches, including cytotoxic agents and molecular-targeted therapies. The most notable feature of immuno-oncology treatments is the nature of the patient responses achieved, which can be more durable and sustained than with other modalities. Increased understanding of immune system complexity has provided a number of opportunities to advance several strategies for the development of immuno-oncology therapies...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28921458/pharmacogenetics-and-pharmacogenomics-in-moderate-to-severe-psoriasis
#13
REVIEW
María C Ovejero-Benito, Ester Muñoz-Aceituno, Alejandra Reolid, Miriam Saiz-Rodríguez, Francisco Abad-Santos, Esteban Daudén
Pharmacogenetics is the study of variations in DNA sequence related to drug response. Moreover, the evolution of biotechnology and the sequencing of human DNA have allowed the creation of pharmacogenomics, a branch of genetics that analyzes human genes, the RNAs and proteins encoded by them, and the inter-and intra-individual variations in expression and function in relation to drug response. Pharmacogenetics and pharmacogenomics are being used to search for biomarkers that can predict response to systemic treatments, including those for moderate-to-severe psoriasis...
September 18, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28919706/profile-of-pembrolizumab-in-the-treatment-of-head-and-neck-squamous-cell-carcinoma-design-development-and-place-in-therapy
#14
REVIEW
Sulsal Haque, Mahender Yellu, Jaskirat Randhawa, Nooshin Hashemi-Sadraei
Head and neck squamous cell cancer (HNSCC) is the sixth most common malignancy worldwide, and despite advances in cytotoxic, surgical and radiation techniques, outcomes are still poor in those with both locally advanced and metastatic diseases. The need for development of better therapeutics along with a greater understanding of the relationship between the immune system and malignancies has led to a new therapeutic modality, immune modulators, particularly checkpoint inhibitors in HNSCC. It is now well recognized that HNSCC circumvents crucial pathways utilized by the immune system to escape surveillance...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28919454/a-robust-immune-system-conditions-the-response-to-abagovomab-anti-idiotypic-monoclonal-antibody-mimicking-the-ca125-protein-vaccination-in-ovarian-cancer-patients
#15
Alessandra Battaglia, Marco Fossati, Alexia Buzzonetti, Giovanni Scambia, Andrea Fattorossi
INTRODUCTION: Despite encouraging phase I and II study results, vaccination of ovarian cancer patients with abagovomab - an anti-idiotypic mAb that mimics the ovarian cancer CA125 protein - failed to demonstrate efficacy in the phase III trial named MIMOSA (NCT00418574). We postulated that in this trial patients with a more robust immune system did respond to abagovomab but went undetected among a larger number of non-responders. We also postulated that assessment of the immune system status ahead of abagovomab administration might predict patients' propensity to respond to abagovomab...
September 14, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28917383/efficacy-and-safety-of-ixekizumab-for-the-treatment-of-moderate-to-severe-plaque-psoriasis-results-through-108%C3%A2-weeks-of-a-randomized-controlled-phase-3-clinical-trial-uncover-3
#16
Andrew Blauvelt, Melinda Gooderham, Lars Iversen, Susan Ball, Lu Zhang, Noah O Agada, Kristian Reich
BACKGROUND: Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin 17A, is efficacious in treating moderate-to-severe plaque psoriasis through 60 weeks. OBJECTIVE: To evaluate the efficacy and safety of ixekizumab through 108 weeks of treatment in UNCOVER-3. METHODS: Patients (N = 1346) were randomized 2:2:2:1 to 80 mg ixekizumab every 2 or 4 weeks, 50 mg etanercept twice weekly, or placebo. At week 12, patients switched to ixekizumab every 4 weeks during a long-term extension (LTE) period...
September 13, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28917265/olaratumab-pdgfr-%C3%AE-inhibition-as-a-novel-tool-in-the-treatment-of-advanced-soft-tissue-sarcomas
#17
REVIEW
Bruno Vincenzi, Giuseppe Badalamenti, Andrea Napolitano, Mariella Spalato Ceruso, Francesco Pantano, Giovanni Grignani, Antonio Russo, Daniele Santini, Massimo Aglietta, Giuseppe Tonini
Advanced soft tissue sarcomas are aggressive cancers with limited therapeutic options. Recently, inhibition of platelet-derived growth factor receptor (PDGFR)-α by the monoclonal antibody olaratumab showed promising clinical activity. If confirmed, this would be one of the first examples of targeted therapy effective in advanced soft tissue sarcomas therapy independently of the histologic subtype. Here, we reviewed the biology of the PDGF/PDGFR axis, particularly focusing on its role in cancer, and then we discussed on the effects of PDGFR-α inhibition in the therapy of advanced soft tissue sarcomas...
October 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28916992/longevity-of-daily-oral-vitamin-d3-supplementation-differences-in-25ohd-and-24-25-oh-2d-observed-2%C3%A2-years-after-cessation-of-a-1-year-randomised-controlled-trial-victory-recall
#18
H M Macdonald, A Gryka, J C Y Tang, L S Aucott, W D Fraser, A D Wood
To determine how long vitamin D lasts after supplementation ceases, the marker of status was measured 2 and 3 years after a 1-year trial. Compared to placebo, the proportion of vitamin D-deficient women was still lower, if they had taken daily vitamin D3, after 2 years, indicating its longevity. INTRODUCTION: The purpose of this study was to determine longevity of vitamin D status following cessation of vitamin D3 supplementation, 2 and 3 years after a 1-year randomised, double-blind placebo controlled trial and to investigate possible predictive factors...
September 15, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28916526/monoclonal-antibodies-directed-against-cadherin-rgd-exhibit-therapeutic-activity-against-melanoma-and-colorectal-cancer-metastasis
#19
Ruben A Bartolomé, Carmen Aizpurua, Marta Jaén, Sofia Torres, Eva Calviño, Juan I Imbaud, J Ignacio Casal
PURPOSE: New targets are required for the control of advanced metastatic disease. We investigated the use of cadherin RGD motifs, which activate the α2β1integrin pathway, as targets for the development of therapeutic monoclonal antibodies (mAbs). EXPERIMENTAL DESIGN: CDH17 fragments and peptides were prepared and used for immunization and antibody development. Antibodies were tested for inhibition of β1 integrin and cell adhesion, proliferation and invasion assays using cell lines from different cancer types: colorectal, pancreatic, melanoma and breast cancer...
September 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28916378/clinical-pharmacology-of-anti-angiogenic-drugs-in-oncology
#20
REVIEW
P Gougis, J Wassermann, J P Spano, N Keynan, C Funck-Brentano, J E Salem
Abnormal vasculature proliferation is one of the so-called hallmarks of cancer. Angiogenesis inhibitor therapies are one of the major breakthroughs in cancer treatment in the last two decades. Two types of anti-angiogenics have been approved: monoclonal antibodies and derivatives, which are injected and target the extracellular part of a receptor, and protein kinase inhibitors, which are orally taken small molecules targeting the intra-cellular Adenosine Triphosphate -pocket of different kinases. They have become an important part of some tumors' treatment, both in monotherapy or in combination...
September 1, 2017: Critical Reviews in Oncology/hematology
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