keyword
MENU ▼
Read by QxMD icon Read
search

Antibody drug conjugates

keyword
https://www.readbyqxmd.com/read/28108597/bispecific-antibodies-and-antibody-drug-conjugates-adcs-bridging-her2-and-prolactin-receptor-improve-efficacy-of-her2-adcs
#1
Julian Andreev, Nithya Thambi, Andres E Perez Bay, Frank J Delfino, Joel H Martin, Marcus P Kelly, Jessica R Kirshner, Ashique Rafique, Arthur Kunz, Thomas Nittoli, Douglas MacDonald, Christopher Daly, William Olson, Gavin Thurston
The properties of cell surface proteins targeted by Antibody-drug conjugates (ADCs) have not been fully exploited; of particular importance are the rate of internalization and the route of intracellular trafficking. In this study we compared the trafficking of HER2, which is the target of the clinically approved ADC ado-trastuzumab emtansine (T-DM1), with that of prolactin receptor (PRLR), another potential target in breast cancer. In contrast to HER2, we found that PRLR is rapidly and constitutively internalized, and traffics efficiently to lysosomes, where it is degraded...
January 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28107624/tocilizumab-alendronate-conjugate-for-treatment-of-rheumatoid-arthritis
#2
Hwiwon Lee, Suk Ho Bhang, Jeong Ho Lee, Hyemin Kim, Sei Kwang Hahn
An autoimmune disease of rheumatoid arthritis (RA) causes severe inflammation on the synovial membrane, which results in the destruction of articular cartilage and bone. Here, Tocilizumab (TCZ) - Alendronate (ALD) conjugate is synthesized for the early intervention of RA. A humanized monoclonal antibody of TCZ shows an immunosuppressive effect, targeting interleukin-6 (IL-6) receptor in the RA pathogenesis. ALD is an anti-inflammatory bisphosphonate drug which can bind to the exposed bone surface. ALD is conjugated selectively to N-glycan on Fc region of TCZ using a chemical linker of 3-(2-pyridyldithio) propionyl hydrazide (PDPH) - poly(ethylene glycol) - N-hydroxysuccinimide (PDPH-PEG-NHS)...
January 20, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28098746/marine-antibody-drug-conjugates-design-strategies-and-research-progress
#3
REVIEW
Yu-Jie Wang, Yu-Yan Li, Xiao-Yu Liu, Xiao-Ling Lu, Xin Cao, Bing-Hua Jiao
Antibody-drug conjugates (ADCs), constructed with monoclonal antibodies (mAbs), linkers, and natural cytotoxins, are innovative drugs developed for oncotherapy. Owing to the distinctive advantages of both chemotherapy drugs and antibody drugs, ADCs have obtained enormous success during the past several years. The development of highly specific antibodies, novel marine toxins' applications, and innovative linker technologies all accelerate the rapid R&D of ADCs. Meanwhile, some challenges remain to be solved for future ADCs...
January 13, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28094575/treatment-approaches-of-hard-to-treat-non-hodgkin-lymphomas
#4
Lakshminarayanan Nandagopal, Amitkumar Mehta
Even after recent advancements with monoclonal antibodies, antibody drug conjugates and immune therapies, relapsed and refractory lymphomas remain challenging to treat; and the definition and treatment approaches of hard-to-treat lymphomas (HTL) continue to evolve. Areas covered: In this review, we will address HTL encompassing diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL) and peripheral T cell lymphomas (PTCL). DLBCL, which comprises 30-40% of non-Hodgkin lymphomas is a highly aggressive and heterogeneous malignancy, with primary refractory or relapsed disease remaining a therapeutic challenge...
January 17, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28092856/separation-of-antibody-drug-conjugate-species-by-rplc-a-generic-method-development-approach
#5
Szabolcs Fekete, Imre Molnár, Davy Guillarme
This study reports the use of modelling software for the successful method development of IgG1 cysteine conjugated antibody drug conjugate (ADC) in RPLC. The goal of such a method is to be able to calculate the average drug to antibody ratio (DAR) of and ADC product. A generic method development strategy was proposed including the optimization of mobile phase temperature, gradient profile and mobile phase ternary composition. For the first time, a 3D retention modelling was presented for large therapeutic protein...
January 11, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28088282/conjugation-site-analysis-of-antibody-drug-conjugates-adcs-by-signature-ion-fingerprinting-and-normalized-area-quantitation-approach-using-nano-liquid-chromatography-coupled-to-high-resolution-mass-spectrometry
#6
Hua Sang, Gaoyuan Lu, Yazhong Liu, Qiyue Hu, Weifeng Xing, Dongbing Cui, Fang Zhou, Jingwei Zhang, Haiping Hao, Guangji Wang, Hui Ye
Trastuzumab-MCC-DM1 (T-DM1) is an antibody-drug conjugate (ADC) that consists of a monoclonal antibody (mAb) trastuzumab non-cleavably linked to a cytotoxic drug DM1. During production, the DM1 agents were conjugated to the lysine residues of the mAb in a non-specific manner, yielding a heterogeneous mixture of ADC molecules that differ with respect to both the number and the conjugation sites of DM1 per mAb molecule. Since drug conjugation sites of ADC can significantly impact properties such as stability and pharmacokinetic behaviors, a rapid and reliable approach for conjugation site analysis of ADCs is highly demanded...
February 22, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28087488/cathepsin-k-targeted-sub-micron-particles-for-regenerative-repair-of-vascular-elastic-matrix
#7
Brenton Jennewine, Jonathan Fox, Anand Ramamurthi
: Abdominal Aortic Aneurysms (AAA) involve slow dilation and weakening of the aortic wall due to breakdown of structural matrix components, such as elastic fibers by chronically overexpressed matrix metalloproteinases (MMPs), primarily, MMPs-2 and -9. Auto-regenerative repair of disrupted elastic fibers by smooth muscle cells (SMCs) at the AAA site is intrinsically poor and together with chronic proteolysis prevents restoration of elastin homeostasis, necessary to enable AAA growth arrest or regression to a healthy state...
January 10, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28077676/a-ptk7-targeted-antibody-drug-conjugate-reduces-tumor-initiating-cells-and-induces-sustained-tumor-regressions
#8
Marc Damelin, Alexander Bankovich, Jeffrey Bernstein, Justin Lucas, Liang Chen, Samuel Williams, Albert Park, Jorge Aguilar, Elana Ernstoff, Manoj Charati, Russell Dushin, Monette Aujay, Christina Lee, Hanna Ramoth, Milly Milton, Johannes Hampl, Sasha Lazetic, Virginia Pulito, Edward Rosfjord, Yongliang Sun, Lindsay King, Frank Barletta, Alison Betts, Magali Guffroy, Hadi Falahatpisheh, Christopher J O'Donnell, Robert Stull, Marybeth Pysz, Paul Escarpe, David Liu, Orit Foord, Hans Peter Gerber, Puja Sapra, Scott J Dylla
Disease relapse after treatment is common in triple-negative breast cancer (TNBC), ovarian cancer (OVCA), and non-small cell lung cancer (NSCLC). Therapies that target tumor-initiating cells (TICs) should improve patient survival by eliminating the cells that can drive tumor recurrence and metastasis. We demonstrate that protein tyrosine kinase 7 (PTK7), a highly conserved but catalytically inactive receptor tyrosine kinase in the Wnt signaling pathway, is enriched on TICs in low-passage TNBC, OVCA, and NSCLC patient-derived xenografts (PDXs)...
January 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28074431/detection-and-specific-elimination-of-egfr-ovarian-cancer-cells-using-a-near-infrared-photoimmunotheranostic-approach
#9
Dirk Bauerschlag, Ivo Meinhold-Heerlein, Nicolai Maass, Andreas Bleilevens, Karen Bräutigam, Wa'el Al Rawashdeh, Stefano Di Fiore, Anke Maria Haugg, Felix Gremse, Julia Steitz, Rainer Fischer, Elmar Stickeler, Stefan Barth, Ahmad Fawzi Hussain
PURPOSE: Targeted theranostics is an alternative strategy in cancer management that aims to improve cancer detection and treatment simultaneously. This approach combines potent therapeutic and diagnostic agents with the specificity of different cell receptor ligands in one product. The success of antibody drug conjugates (ADCs) in clinical practice has encouraged the development of antibody theranostics conjugates (ATCs). However, the generation of homogeneous and pharmaceutically-acceptable ATCs remains a major challenge...
January 10, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28070718/first-in-human-trial-of-an-anti-5t4-antibody-monomethylauristatin-conjugate-pf-06263507-in-patients-with-advanced-solid-tumors
#10
Geoffrey I Shapiro, Ulka N Vaishampayan, Patricia LoRusso, Jeremy Barton, Steven Hua, Steven D Reich, Ronald Shazer, Carrie T Taylor, Dawei Xuan, Hossein Borghaei
Background The antibody-drug conjugate PF-06263507 targets the cell-surface, tumor-associated antigen 5T4 and consists of a humanized IgG1 conjugated to the microtubule-disrupting agent monomethylauristatin-F by a non-cleavable maleimidocaproyl linker. In this first-in-human, dose-finding trial (NCT01891669), we evaluated safety, pharmacokinetics, and preliminary antitumor activity of PF-06263507 in pretreated patients with advanced solid tumors, unselected for 5T4 expression. starting at 0.05 mg/kg, with 25, 56, and 95% dose increments, depending on observed dose-limiting toxicities (DLTs), applying a modified continual reassessment method...
January 9, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28069724/synthetic-lethality-exploitation-by-an-anti-trop-2-sn-38-antibody-drug-conjugate-immu-132-plus-parp-inhibitors-in-brca1-2-wild-type-triple-negative-breast-cancer
#11
Thomas M Cardillo, Robert M Sharkey, Diane L Rossi, Roberto Arrojo, Ali Mostafa, David M Goldenberg
PURPOSE: Both Poly(ADP-ribose) polymerase inhibitors (PARPi) and sacituzumab govitecan (IMMU-132) are currently under clinical evaluation in triple-negative breast cancer (TNBC). We sought to investigate the combined DNA-damaging effects of the topoisomerase I (Topo I)-inhibitory activity of IMMU-132 with PARPi disruption of DNA repair in TNBC. EXPERIMENTAL DESIGN: In vitro, human TNBC cell lines were incubated with IMMU-132 and various PARPi (olaparib, rucaparib, or talazoparib) to determine the effect on growth, double-stranded DNA (dsDNA) breaks, and cell-cycle arrest...
January 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28067204/cd9-monoclonal-antibody-conjugated-pegylated-liposomes-for-targeted-delivery-of-rapamycin-in-the-treatment-of-cellular-senescence
#12
Hanh Thuy Nguyen, Raj Kumar Thapa, Beom Soo Shin, Jee-Heon Jeong, Jae-Ryong Kim, Chul Soon Yong, Jong Oh Kim
Premature cellular senescence refers to the state of irreversible cell cycle arrest due to DNA damage or other stresses. In this study, CD9 monoclonal antibody (CD9mAb) was successfully conjugated to the surface of PEGylated liposomes for targeted delivery of rapamycin (LR-CD9mAb) to overcome senescence of CD9 receptor-overexpressing cells. LR-CD9mAb has a small particle size (143.3 �� 2.4 nm), narrow size distribution (polydispersity index: 0.220 �� 0.036), and negative zeta potential (���14...
January 9, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28062707/optimization-of-a-pegylated-glucuronide-monomethylauristatin-e-linker-for-antibody-drug-conjugates
#13
Patrick J Burke, Joseph Z Hamilton, Scott C Jeffrey, Joshua H Hunter, Svetlana O Doronina, Nicole M Okeley, Jamie B Miyamoto, Martha E Anderson, Ivan J Stone, Michelle L Ulrich, Jessica K Simmons, Erica E McKinney, Peter D Senter, Robert P Lyon
The emergence of antibody-drug conjugates (ADC), such as brentuximab vedotin and ado-trastuzumab emtansine, has led to increased efforts to identify new payloads and develop improved drug-linker technologies. Most antibody payloads impart significant hydrophobicity to the ADC, resulting in accelerated plasma clearance and suboptimal in vivo activity, particularly for conjugates with high drug-to-antibody ratios (DAR). We recently reported on the incorporation of a discrete PEG24 polymer as a side chain in a β-glucuronidase-cleavable monomethylauristatin E (MMAE) linker to provide homogeneous DAR 8 conjugates with decreased plasma clearance and increased antitumor activity in xenograft models relative to a non-PEGylated control...
January 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28062477/imgn853-is-active-in-patients-with-fr%C3%AE-positive-ovarian-cancer
#14
(no author information available yet)
A FRα-targeting antibody-drug conjugate induces responses in patients with platinum-resistant tumors.
January 6, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28060485/investigation-of-hydrophilic-auristatin-derivatives-for-use-in-antibody-drug-conjugates
#15
Brian A Mendelsohn, Stuart D Barnscher, Josh T Snyder, Zili An, Jennifer M Dodd, Julien Dugal-Tessier
Antibody drug conjugates offer a targeted cancer treatment for the delivery of potent cytotoxic drugs. Derivatives of the natural product dolastatin 10 containing pyridines and other basic amines were examined with the objective of determining if a more hydrophilic auristatin derivative would be potent enough for use as part of an ADC. This may be advantageous if a less hydrophobic drug makes a better ADC. A pyridine derivative, monomethyl auristatin PYE, showed the greatest potency when tested in vivo. While only a modest tumor growth inhibition was observed when the HCC1954 human breast cancer xenografts were treated with"non-cleavable" linker ADCs, tumor regression was seen when treated with an enzymatically degradable "cleavable" linker ADC when conjugated to trastuzumab...
January 6, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28060353/efficient-and-site-specific-antibody-labeling-by-strain-promoted-azide-alkyne-cycloaddition
#16
Sanggil Kim, Wooseok Ko, Hyunji Park, Hyun Soo Lee
There are currently many chemical tools available to introduce chemical probes into proteins to study their structure and function. A useful method is protein conjugation by genetically introducing an unnatural amino acid containing a bioorthogonal functional group. This report describes a detailed protocol for site-specific antibody conjugation. The protocol includes experimental details for the genetic incorporation of an azide-containing amino acid, and the conjugation reaction by strain-promoted azide-alkyne cycloaddition (SPAAC)...
December 23, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28056739/from-natural-products-to-designer-drugs-development-and-molecular-mechanisms-of-action-of-novel-anti-microtubule-breast-cancer-therapeutics
#17
Tejashree Mahaddalkar, Manu Lopus
Microtubule-targeted drugs (MTDs) have been on the forefront of breast cancer chemotherapy. Classic MTDs, such as paclitaxel and their semisynthetic derivatives, have achieved considerable success in the clinical management of breast neoplasms. In order to improve the specificity and to reduce undesirable, dose-limiting toxicities of these drugs, a plethora of novel compounds are being synthesized and investigated in laboratories worldwide. Due to their crucial roles during cell division, and to the fact that the suppression of their innate 'dynamic instability' can arrest cell cycle progression, microtubules formed an attractive target for cancer chemotherapy...
4, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28056202/trastuzumab-emtansine-with-or-without-pertuzumab-versus-trastuzumab-plus-taxane-for-human-epidermal-growth-factor-receptor-2-positive-advanced-breast-cancer-primary-results-from-the-phase-iii-marianne-study
#18
Edith A Perez, Carlos Barrios, Wolfgang Eiermann, Masakazu Toi, Young-Hyuck Im, Pierfranco Conte, Miguel Martin, Tadeusz Pienkowski, Xavier Pivot, Howard Burris, Jennifer A Petersen, Sven Stanzel, Alexander Strasak, Monika Patre, Paul Ellis
Purpose Trastuzumab and pertuzumab are human epidermal growth factor receptor 2 (HER2) -targeted monoclonal antibodies, and trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that combines the properties of trastuzumab with the cytotoxic activity of DM1. T-DM1 demonstrated encouraging efficacy and safety in a phase II study of patients with previously untreated HER2-positive metastatic breast cancer. Combination T-DM1 and pertuzumab showed synergistic activity in cell culture models and had an acceptable safety profile in a phase Ib and II study...
January 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28045502/legomedicine-a-versatile-chemo-enzymatic-approach-for-the-preparation-of-targeted-dual-labeled-llama-antibody-nanoparticle-conjugates
#19
Sanne A M van Lith, Sander M J van Duijnhoven, Anna C Navis, Edward Dolk, Jos W H Wennink, Cornelus F van Nostrum, Jan C M van Hest, William P J Leenders, Sanne A M van Lith, Sander M J van Duijnhoven, Anna C Navis, William P J Leenders, Edward Dolk, Jos W H Wennink, Cornelus F van Nostrum, Jan C M van Hest
Conjugation of llama single domain antibody fragments (Variable Heavy chain domains of Heavy chain antibodies, VHHs) to diagnostic or therapeutic nanoparticles, peptides, proteins, or drugs offers many opportunities for optimized targeted cancer treatment. Currently, mostly nonspecific conjugation strategies or genetic fusions are used that may compromise VHH functionality. In this paper we present a versatile modular approach for bioorthogonal VHH modification and conjugation. First, sortase A mediated transPEGylation is used for introduction of a chemical click moiety...
January 18, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28039367/efficacy-and-safety-results-of-abt-414-in-combination-with-radiation-and-temozolomide-in-newly-diagnosed-glioblastoma
#20
David A Reardon, Andrew B Lassman, Martin van den Bent, Priya Kumthekar, Ryan Merrell, Andrew M Scott, Lisa Fichtel, Erik P Sulman, Erica Gomez, JuDee Fischer, Ho-Jin Lee, Wijith Munasinghe, Hao Xiong, Helen Mandich, Lisa Roberts-Rapp, Peter Ansell, Kyle D Holen, Hui K Gan
BACKGROUND: The purpose of this study was to determine the maximum tolerated dose (MTD), recommended phase II dose (RPTD), safety, and pharmacokinetics of ABT-414 plus radiation and temozolomide in newly diagnosed glioblastoma. ABT-414 is a first-in-class, tumor-specific antibody-drug conjugate that preferentially targets tumors expressing overactive epidermal growth factor receptor (EGFR). METHODS: In this multicenter phase I study, patients received 0.5-3.2 mg/kg ABT-414 every 2 weeks by intravenous infusion...
December 29, 2016: Neuro-oncology
keyword
keyword
49557
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"