keyword
MENU ▼
Read by QxMD icon Read
search

Antibody-Drug Conjugate

keyword
https://www.readbyqxmd.com/read/28087488/cathepsin-k-targeted-sub-micron-particles-for-regenerative-repair-of-vascular-elastic-matrix
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
(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
#9
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
#10
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
#11
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
#12
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
#13
Sanne Anna Maria 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
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 3, 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
#14
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
https://www.readbyqxmd.com/read/28034806/targeting-the-extracellular-matrix-of-ovarian-cancer-using-functionalized-drug-loaded-lyophilisomes
#15
Sophieke C H A van der Steen, René Raavé, Sjoerd Langerak, Laurens van Houdt, Sander M J van Duijnhoven, Sanne A M van Lith, Leon F A G Massuger, Willeke F Daamen, William P Leenders, Toin H van Kuppevelt
Epithelial ovarian cancer is characterized by a high mortality rate and is in need for novel therapeutic avenues to improve patient outcome. The tumor's extracellular matrix ("stroma") offers new possibilities for targeted drug-delivery. Recently we identified highly sulfated chondroitin sulfate (CS-E) as a component abundantly present in the ovarian cancer extracellular matrix, and as an novel target for anti-cancer therapy. Here, we report on the functionalization of drug-loaded lyophilisomes (albumin-based biocapsules) to specifically target the stroma of ovarian carcinomas with the potential to eliminate cancer cells...
December 26, 2016: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28029313/safety-and-activity-of-mirvetuximab-soravtansine-imgn853-a-folate-receptor-alpha-targeting-antibody-drug-conjugate-in-platinum-resistant-ovarian-fallopian-tube-or-primary-peritoneal-cancer-a-phase-i-expansion-study
#16
Kathleen N Moore, Lainie P Martin, David M O'Malley, Ursula A Matulonis, Jason A Konner, Raymond P Perez, Todd M Bauer, Rodrigo Ruiz-Soto, Michael J Birrer
Purpose This phase I expansion cohort study evaluated the safety and clinical activity of mirvetuximab soravtansine (IMGN853), an antibody-drug conjugate consisting of a humanized anti-folate receptor alpha (FRα) monoclonal antibody linked to the tubulin-disrupting maytansinoid DM4, in a population of patients with FRα-positive and platinum-resistant ovarian cancer. Patients and Methods Patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer received IMGN853 at 6...
December 28, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28024916/drug-free-macromolecular-therapeutics-impact-of-structure-on-induction-of-apoptosis-in-raji-b-cells
#17
Libin Zhang, Yixin Fang, Jiyuan Yang, Jindřich Kopeček
Recently, we developed a new paradigm in macromolecular therapeutics that avoids the use of low molecular weight drugs. The activity of the "drug-free macromolecular therapeutics" is based on the biorecognition of complementary motifs at cell surface resulting in receptor crosslinking and apoptosis induction. The system is composed of two nanoconjugates: (1) a single-stranded morpholino oligonucleotide (MORF1) attached to an anti-CD20 Fab' fragment (Fab'-MORF1); (2) multiple copies of complementary oligonucleotide MORF2 grafted to a linear polymer of N-(2-hydroxypropyl)methacrylamide (HPMA) - P-(MORF2)x...
December 23, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28018954/regression-of-metastatic-radiation-chemotherapy-resistant-uterine-serous-carcinoma-overexpressing-her2-neu-with-trastuzumab-emtansine-tdm-1
#18
Alessandro D Santin, Stefania Bellone, Natalia Buza, Peter E Schwartz
BACKGROUND: The management of uterine-serous-carcinoma (USC) no longer amenable to treatment with surgery, radiation and/or chemotherapy remains dismal. Alternative therapeutic options are desperately needed. CASE: We describe the case of a heavily pretreated 74-year-old patient with a recurrent USC overexpressing HER2/neu at 3 + level by IHC treated with the anti-HER2/neu antibody-drug-conjugate (ADC) trastuzumab-emtansine (TDM-1-Kadcyla-Genentech/Roche). She experienced a remarkable clinical response to TDM-1 with a complete resolution of a large metastatic, radiation/chemotherapy resistant tumor deposit in her abdominal wall muscle confirmed by multiple CAT scans and a prolonged systemic control of her disease...
February 2017: Gynecologic Oncology Reports
https://www.readbyqxmd.com/read/28017567/drug-to-antibody-determination-for-an-antibody-drug-conjugate-utilizing-cathepsin-b-digestion-coupled-with-reversed-phase-high-pressure-liquid-chromatography-analysis
#19
Michael Adamo, Guoyong Sun, Difei Qiu, Joseph Valente, Wenkui Lan, Hangtian Song, Mark Bolgar, Amit Katiyar, Girija Krishnamurthy
Antibody drug conjugates or ADCs are currently being evaluated for their effectiveness as targeted chemotherapeutic agents across the pharmaceutical industry. Due to the complexity arising from the choice of antibody, drug and linker; analytical methods for release and stability testing are required to provide a detailed understanding of both the antibody and the drug during manufacturing and storage. The ADC analyzed in this work consists of a tubulysin drug analogue that is randomly conjugated to lysine residues in a human IgG1 antibody...
December 19, 2016: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28017562/optimization-of-non-linear-gradient-in-hydrophobic-interaction-chromatography-for-the-analytical-characterization-of-antibody-drug-conjugates
#20
Balázs Bobály, Giuseppe Marco Randazzo, Serge Rudaz, Davy Guillarme, Szabolcs Fekete
The goal of this work was to evaluate the potential of non-linear gradients in hydrophobic interaction chromatography (HIC), to improve the separation between the different homologous species (drug-to-antibody, DAR) of commercial antibody-drug conjugates (ADC). The selectivities between Brentuximab Vedotin species were measured using three different gradient profiles, namely linear, power function based and logarithmic ones. The logarithmic gradient provides the most equidistant retention distribution for the DAR species and offers the best overall separation of cysteine linked ADC in HIC...
December 16, 2016: Journal of Chromatography. A
keyword
keyword
41102
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"