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Antibody-Drug Conjugate

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https://www.readbyqxmd.com/read/28230204/high-resolution-imaging-of-living-mammalian-cells-bound-by-nanobeads-connected-antibodies-in-a-medium-using-scanning-electron-assisted-dielectric-microscopy
#1
Tomoko Okada, Toshihiko Ogura
Nanometre-scale-resolution imaging technologies for liquid-phase specimens are indispensable tools in various scientific fields. In biology, observing untreated living cells in a medium is essential for analysing cellular functions. However, nanoparticles that bind living cells in a medium are hard to detect directly using traditional optical or electron microscopy. Therefore, we previously developed a novel scanning electron-assisted dielectric microscope (SE-ADM) capable of nanoscale observations. This method enables observation of intact cells in aqueous conditions...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28224235/oral-mucosal-changes-induced-by-anticancer-targeted-therapies-and-immune-checkpoint-inhibitors
#2
REVIEW
Emmanuelle Vigarios, Joel B Epstein, Vincent Sibaud
Development of biological targeted therapies and immune checkpoint inhibitors has redefined the treatment for many cancers; however, the increasing use of new protocols has led to physicians observing a new spectrum of toxicities. To date, oral adverse events induced by these new anticancer therapies have been mainly reported using nonspecific terminology ("stomatitis," "mucosal inflammation," "mucositis") and remain poorly characterized, with the exception of mammalian target of rapamycin (mTOR) inhibitor-associated stomatitis...
February 22, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28223423/modulating-therapeutic-activity-and-toxicity-of-pyrrolobenzodiazepine-antibody-drug-conjugates-with-self-immolative-disulfide-linkers
#3
Thomas H Pillow, Melissa Schutten, Shang-Fan Yu, Rachana Ohri, Jack Sadowsky, Kirsten Achilles Poon, Willy Solis, Fiona Zhong, Geoffrey Del Rosario, Mary Ann T Go, Jeffery Lau, Sharon Yee, Jintang He, Luna Liu, Carl Ng, Keyang Xu, Douglas D Leipold, Amrita V Kamath, Donglu Zhang, Luke Masterson, Stephen J Gregson, Philip W Howard, Fan Fang, Jinhua Chen, Janet Gunzner-Toste, Katherine K Kozak, Susan Spencer, Paul Polakis, Andrew G Polson, John A Flygare, Jagath R Junutula
A novel disulfide linker was designed to enable a direct connection between cytotoxic pyrrolobenzodiazepine (PBD) drugs and the cysteine on a targeting antibody for use in antibody-drug conjugates (ADCs). ADCs composed of a cysteine-engineered antibody were armed with a PBD using a self-immolative disulfide linker. Both the chemical linker and the antibody site were optimized for this new bioconjugation strategy to provide a highly stable and efficacious ADC. This novel disulfide ADC was compared to a conjugate containing the same PBD drug, but attached to the antibody via a peptide linker...
February 21, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28216573/a-conjugate-based-on-anti-her2-diaffibody-and-auristatin-e-targets-her2-positive-cancer-cells
#4
Anna M Serwotka-Suszczak, Alicja M Sochaj-Gregorczyk, Jerzy Pieczykolan, Daniel Krowarsch, Filip Jelen, Jacek Otlewski
Antibody-drug conjugates (ADCs) have recently emerged as efficient and selective cancer treatment therapeutics. Currently, alternative forms of drug carriers that can replace monoclonal antibodies are under intensive investigation. Here, a cytotoxic conjugate of an anti-HER2 (Human Epidermal Growth Factor Receptor 2) diaffibody with monomethyl-auristatin E (MMAE) is proposed as a potential anticancer therapeutic. The anti-HER2 diaffibody was based on the ZHER2:4 affibody amino acid sequence. The anti-HER2 diaffibody has been expressed as a His-tagged protein in E...
February 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28212584/hyaluronic-acid-serum-albumin-conjugate-based-nanoparticles-for-targeted-cancer-therapy
#5
Ravit Edelman, Yehuda G Assaraf, Inna Levitzky, Tal Shahar, Yoav D Livney
Multiple carcinomas including breast, ovarian, colon, lung and stomach cancer, overexpress the hyaluronic acid (HA) receptor, CD44. Overexpression of CD44 contributes to key cancer processes including tumor invasion, metastasis, recurrence, and chemoresistance. Herein, we devised novel targeted nanoparticles (NPs) for delivery of anticancer chemotherapeutics, comprised of self-assembling Maillard reaction-based conjugates of HA and bovine serum albumin (BSA). HA served as the hydrophilic block, and as the ligand for actively targeting cancer cells overexpressing CD44...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212575/upregulation-of-mucin-glycoprotein-muc1-in-the-progression-to-esophageal-adenocarcinoma-and-therapeutic-potential-with-a-targeted-photoactive-antibody-drug-conjugate
#6
Mohammed Adil Butt, Hayley Pye, Rehan J Haidry, Dahmane Oukrif, Saif-U-Rehman Khan, Ignazio Puccio, Michael Gandy, Halla W Reinert, Ellie Bloom, Mohammed Rashid, Gokhan Yahioglu, Mahendra P Deonarain, Rifat Hamoudi, Manuel Rodriguez-Justo, Marco R Novelli, Laurence B Lovat
BACKGROUND: Mucin glycoprotein 1 (MUC1) is a glycosylated transmembrane protein on epithelial cells. We investigate MUC1 as a therapeutic target in Barrett's epithelium (BE) and esophageal adenocarcinoma (EA) and provide proof of concept for a light based therapy targeting MUC1. RESULTS: MUC1 was present in 21% and 30% of significantly enriched pathways comparing BE and EA to squamous epithelium respectively. MUC1 gene expression was x2.3 and x2.2 higher in BE (p=<0...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28211613/novel-anticarcinoembryonic-antigen-antibody-drug-conjugate-has-antitumor-activity-in-the-existence-of-soluble-antigen
#7
Daisuke Shinmi, Ryosuke Nakano, Keisuke Mitamura, Minami Suzuki-Imaizumi, Junko Iwano, Yuya Isoda, Junichi Enokizono, Yasuhisa Shiraishi, Emi Arakawa, Kazuma Tomizuka, Kazuhiro Masuda
Carcinoembryonic antigen (CEA) is a classic tumor-specific antigen that is overexpressed in several cancers, including gastric cancer. Although some anti-CEA antibodies have been tested, to the best of our knowledge, there are currently no clinically approved anti-CEA antibody therapies. Because of this, we have created the novel anti-CEA antibody, 15-1-32, which exhibits stronger binding to membrane-bound CEA on cancer cells than existing anti-CEA antibodies. 15-1-32 also shows poor affinity for soluble CEA; thus, the binding activity of 15-1-32 to membrane-bound CEA is not influenced by soluble CEA...
February 17, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28211277/antineoplastic-agents-603-quinstatins-exceptional-cancer-cell-growth-inhibitors
#8
George R Pettit, Noeleen Melody, Jean-Charles Chapuis
Discovery of the exceptionally powerful anticancer drug dolastatin 10 (1), contained in the sea hare Dolabella auricularia, opened a new frontier needed for improving human cancer treatment. Subsequently, major advances have been achieved based on results of structurally modifying this unusual natural peptide while maintaining the remarkable anticancer activity necessary for preparation of successful monoclonal antibody drug conjugates (ADC). Among the first several hundred SAR products based on dolastatin 10 our group synthesized and termed auristatins was auristatin E (2a)...
February 17, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28210462/accuracy-of-a-new-rapid-antigen-detection-test-for-pulmonary-tuberculosis
#9
Rasoul Aliannejad, Ahmadreza Bahrmand, Hamidreza Abtahi, Mahnaz Seifi, Enayat Safavi, Farid Abdolrahimi, Shahriyar Shahriaran
BACKGROUND AND OBJECTIVES: Tuberculosis (TB) is a major problem in the world. Treatment and control of TB needs detection of the Mycobacterium tuberculosis (MT) in the proper samples. While smear doesn't have enough sensitivity, culture and PCR are expensive, time consuming and unavailable in many centers. Recent development of a rapid TB antigen detection test (PrTBK) at Pasteur Institute of Iran could give a simple way for diagnosis of TB in about two hours. In this test the antigen-antibody complex will change color when gold conjugated mouse anti-rabbit antibody detects specific MT cell wall antigen in suspected samples...
August 2016: Iranian Journal of Microbiology
https://www.readbyqxmd.com/read/28205193/new-therapeutic-strategies-for-triple-negative-breast-cancer
#10
REVIEW
Borbála Székely, Andrea L M Silber, Lajos Pusztai
Relatively few clinically important therapeutic advances have occurred in the treatment of triple-negative breast cancer (TNBC) since the introduction of taxanes as adjuvant therapy over 20 years ago. However, this is rapidly changing due to a variety of conceptually important clinical trials and emerging new options such as immune checkpoint inhibitors and antibody-drug conjugates. Evidence also increasingly supports that platinum drugs and inhibitors of poly (ADP-ribose) polymerase, or PARP, are particularly effective in the treatment of germline BRCA-mutant cancers, including TNBC...
February 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28193011/optimization-of-an-anti-poly-ethylene-glycol-anti-peg-cell-based-capture-system-to-quantify-peg-and-pegylated-molecules
#11
Wen-Wei Lin, Yuan-Chin Hsieh, Yi-An Cheng, Kuo-Hsiang Chuang, Chien-Chiao Huang, Chih-Hung Chuang, I-Ju Chen, Kai-Wen Cheng, Yun-Chi Lu, Ta-Chun Cheng, Yeng-Tseng Wang, Steve R Roffler, Tian-Lu Cheng
Sensitive determination of the pharmacokinetics of PEGylated molecules can accelerate the process of drug development. Here, we combined different anti-PEG Fab expressing 293T cells as capture cells (293T/3.3, 293T/6.3, and 293T/15-2b cells) with four detective anti-PEG antibodies (3.3, 6.3, 7A4, or 15-2b) to optimize an anti-PEG cell-based sandwich ELISA. Then, we quantified free PEG (mPEG2K-NH2 and mPEG5K-NH2) or PEG-conjugated small molecules (mPEG5K-biotin and mPEG5K-NIR797), proteins (PegIntron and Pegasys), and nanoparticles (Liposomal-Doxorubicin and quantum-dots)...
December 20, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/28191936/development-of-fluorophore-labeled-thailanstatin-antibody-drug-conjugates-for-cellular-trafficking-studies
#12
Chethana Kulkarni, James E Finley, Andrew J Bessire, Xiaotian Zhong, Sylvia Musto, Edmund Idris Graziani
As the antibody-drug conjugate (ADC) field grows increasingly important for cancer treatment, it is vital for researchers to establish a firm understanding of how ADCs function at the molecular level. To gain insight into ADC uptake, trafficking, and catabolism-processes that are critical to ADC efficacy and toxicity-imaging studies have been performed with fluorophore-labeled conjugates. However, such labels may alter the properties and behavior of the ADC under investigation. As an alternative approach, we present here the development of a "clickable" ADC bearing an azide-functionalized linker-payload (LP) poised for "click" reaction with alkyne fluorophores; the azide group represents a significantly smaller structural perturbation to the LP than most fluorophores...
February 13, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28188407/phase-ii-study-of-the-antibody-drug-conjugate-tak-264-mln0264-in-patients-with-metastatic-or-recurrent-adenocarcinoma-of-the-stomach-or-gastroesophageal-junction-expressing-guanylyl-cyclase-c
#13
Khaldoun Almhanna, Maria Luisa Limon Miron, David Wright, Antonio Cubillo Gracian, Richard A Hubner, Jean-Luc Van Laethem, Carolina Muriel López, Maria Alsina, Frederico Longo Muñoz, Johanna Bendell, Irfan Firdaus, Wells Messersmith, Zhan Ye, Adedigbo A Fasanmade, Hadi Danaee, Thea Kalebic
Background The first-in-class antibody-drug conjugate TAK-264 (formerly MLN0264) consists of an antibody targeting guanylyl cyclase C (GCC) conjugated to monomethyl auristatin E (MMAE) via a peptide linker. This phase II study evaluated the efficacy and safety of TAK-264 in patients with adenocarcinoma of the stomach or gastroesophageal junction expressing GCC, who had progressed on ≥1 line of prior therapy. Methods This study used a two-stage design, with an interim analysis conducted after stage I to determine whether to continue to stage II or discontinue on the grounds of futility...
February 11, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28188066/synthesis-and-in-vitro-evaluation-of-sg3227-a-pyrrolobenzodiazepine-dimer-antibody-drug-conjugate-payload-based-on-sibiromycin
#14
Gary C Kemp, Arnaud C Tiberghien, Neki V Patel, Francois D'Hooge, Sanjay M Nilapwar, Lauren R Adams, Simon Corbett, David G Williams, John A Hartley, Philip W Howard
A novel pyrrolobenzodiazepine dimer payload, SG3227, was rationally designed based on the naturally occurring antitumour compound sibiromycin. SG3227 was synthesized from a dimeric core in an efficient fashion. An unexpected room temperature Diels-Alder reaction occurred during the final step of the synthesis and was circumvented by use of an iodoacetamide conjugation moiety in place of a maleimide. The payload was successfully conjugated to trastuzumab and the resulting ADC exhibited potent activity against a HER2-expressing human cancer cell line in vitro...
January 30, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28187445/in-vivo-histone-h1-migration-from-necrotic-to-viable-tissue
#15
Keith A Luhrs, Desmond Pink, Wendy Schulte, Andries Zijlstra, John D Lewis, Missag H Parseghian
Necrosis is induced by ischemic conditions within the core of many solid tumors. Using fluorescent fusion proteins, we provide in vivo evidence of histone trafficking among cancer cells in implanted tumors. In particular, the most abundant H1 isoform (H1.2) was found to be transported from necrotic tumor cells into surrounding viable cells where histones are selectively taken up by energy-dependent endocytosis. We propose that intercellular histone trafficking could function as a target for drug delivery. This concept was validated using an anti-histone antibody that was co-internalized with histones from dead cells into viable ones surrounding the necrotic regions of a tumor, where some of the most chemoresistant cells reside...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28183972/redox-based-reagents-for-chemoselective-methionine-bioconjugation
#16
Shixian Lin, Xiaoyu Yang, Shang Jia, Amy M Weeks, Michael Hornsby, Peter S Lee, Rita V Nichiporuk, Anthony T Iavarone, James A Wells, F Dean Toste, Christopher J Chang
Cysteine can be specifically functionalized by a myriad of acid-base conjugation strategies for applications ranging from probing protein function to antibody-drug conjugates and proteomics. In contrast, selective ligation to the other sulfur-containing amino acid, methionine, has been precluded by its intrinsically weaker nucleophilicity. Here, we report a strategy for chemoselective methionine bioconjugation through redox reactivity, using oxaziridine-based reagents to achieve highly selective, rapid, and robust methionine labeling under a range of biocompatible reaction conditions...
February 10, 2017: Science
https://www.readbyqxmd.com/read/28170265/immunoprotein-mediated-sirna-delivery
#17
Nicole Bäumer, Wolfgang E Berdel, Sebastian Bäumer
RNA interference strategies offer an alternative to small molecular drug targeting. Small interfering RNA (siRNA) constitutes a class of molecules that allows the effective and specific inhibition of the biosynthesis of any protein. Indeed, siRNA have emerged as a major tool in molecular biology techniques and an important approach to identify suitable therapy targets in cancer. However, siRNA therapy approaches in vivo are scarce. Two major problems hinder siRNA as a therapeutic tool: (1) delivery through the bloodstream leads to degradation or rapid renal clearance (stabilization) and (2) specific uptake by the desired cell type (specificity)...
February 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28165814/targeting-delivery-of-simvastatin-using-icam-1-antibody-conjugated-nanostructured-lipid-carriers-for-acute-lung-injury-therapy
#18
Shu-Juan Li, Xiao-Juan Wang, Jing-Bo Hu, Xu-Qi Kang, Li Chen, Xiao-Ling Xu, Xiao-Ying Ying, Sai-Ping Jiang, Yong-Zhong Du
Acute lung injury (ALI) is a critical illness without effective therapeutic modalities currently. Recent studies indicated potential efficacy of statins for ALI, while high-dose statins was suggested to be significant for attenuating inflammation in vivo. Therefore, a lung-targeted drug delivery system (DDS) delivering simvastatin (SV) for ALI therapy was developed, attempting to improve the disease with a decreased dose and minimize potential adverse effects. SV-loaded nanostructured lipid carriers (SV/NLCs) with different size were prepared primarily...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28161682/preclinical-evaluation-of-taxane-binding-peptide-modified-polymeric-micelles-loaded-with-docetaxel-in-an-orthotopic-breast-cancer-mouse-model
#19
Jennifer Logie, Ahil N Ganesh, Ahmed M Aman, Rima S Al-Awar, Molly S Shoichet
We developed a novel taxane-binding peptide (TBP) modified, biodegradable polymeric micelle that overcomes limitations of drug loading and poor serum stability typically seen with particle delivery, leading to enhanced pharmacokinetics and tumor distribution of docetaxel (DTX). The use of the taxane-binding peptide to increase docetaxel loading is particularly compelling as it takes advantage of a known intracellular binding mechanism in a new way. Docetaxel is a potent chemotherapeutic with a therapeutic index often limited by the toxicity of the excipients that are necessary to enhance its solubility for intravenous delivery...
January 26, 2017: Biomaterials
https://www.readbyqxmd.com/read/28160550/dysadherin-specific-drug-conjugates-for-the-treatment-of-thyroid-cancers-with-aggressive-phenotypes
#20
Samuel Jang, Xiao-Min Yu, Celina Montemayor-Garcia, Kamal Ahmed, Eric Weinlander, Ricardo V Lloyd, Ajitha Dammalapati, David Marshall, James R Prudent, Herbert Chen
BACKGROUND: EDC1 is a novel type of antibody-drug conjugate which binds and inhibits the Na,K-ATPase on the surface of cancer cells expressing dysadherin. The purpose of this study was to determine the expression of dysadherin in different types of thyroid carcinoma, and evaluate the therapeutic potential of EDC1 for thyroid carcinomas. METHODS: Thyroid tissues from 158 patients were examined for dysadherin expression and correlation with clinicopathological features...
January 30, 2017: Oncotarget
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