Corporate Banner
Satellite Banner
Scientific Communities
Become a Member | Sign in
Home>News>This Article

ADME of Antibody-Maytansinoid Conjugates

Published: Wednesday, August 20, 2014
Last Updated: Wednesday, August 20, 2014
Bookmark and Share
Continued understanding of the ADME properties of ADCs entering clinical evaluations should provide additional insight into attributes that may be necessary for clinical success.

The concept of treating cancer with antibody-drug conjugates (ADCs) has gained momentum with the favorable activity and safety of trastuzumab emtansine (T-DM1), SAR3419, and lorvotuzumab mertansine (IMGN901). All three ADCs utilize maytansinoid cell-killing agents which target tubulin and suppress microtubule dynamics. Each ADC utilizes a different optimized chemical linker to attach the maytansinoid to the antibody. Characterizing the absorption, distribution, metabolism, and excretion (ADME) of these ADCs in preclinical animal models is important to understanding their efficacy and safety profiles. The ADME properties of these ADCs in rodents were inferred from studies with radio-labeled ADCs prepared with nonbinding antibodies since T-DM1, SAR3419, IMGN901 all lack cross-reactivity with rodent antigens. For studies exploring tumor localization and activation in tumor-bearing mice, tritium-labeled T-DM1, SAR3419, and IMGN901 were utilized. The chemical nature of the linker was found to have a significant impact on the ADME properties of these ADCs-particularly on the plasma pharmacokinetics and observed catabolites in tumor and liver tissues. Despite these differences, T-DM1, SAR3419, and IMGN901 were all found to facilitate efficient deliveries of active maytansinoid catabolites to the tumor tissue in mouse xenograft models. In addition, all three ADCs were effectively detoxified during hepatobiliary elimination in rodents.

The review article is published online in The AAPS Journal and is free to access. 

Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,500+ scientific posters on ePosters
  • More Than 5,200+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Targeting Cannabinoid CB2 Receptors in the CNS
With endogenous cannabinoids considered as a potential target to combat CNS diseases, this article examines the role of CB2R could play in fighting some disorders.
Wednesday, October 19, 2016
Food Analysis Applications of Core-Shell Columns in HPLC
Despite applications of core-shell particles columns in food analysis being at an early stage, articles describing their use for improving separations of several classes of compounds are becoming more frequent.
Wednesday, October 19, 2016
Porphyrins as Catalysts in Scalable Organic Reactions
This review covers the most relevant scalable porphyrin-catalysed procedures, showing how these compounds represent broad applications in chemistry.
Tuesday, July 26, 2016
Determination of 13 Organic Toxicants in Human Blood
Researchers have utilised liquid-liquid extraction coupling HPLC-MS/MS to identify and quantify organic toxicants in human blood.
Friday, July 22, 2016
A Novel Cell Culture Model For Forensic Biology Experiments
Researchers have developed a new cell culture model which provides an efficient research tool in forensic biology.
Friday, July 22, 2016
Gender Determination in Forensic Investigations
This study investigated the effectiveness of lip print analysis as a tool in gender determination.
Friday, June 24, 2016
Plasma Biomarkers for Breast Cancer Diagnosis
Plasma lipidomics profiling identified lipid biomarkers in distinguishing early-stage breast cancer from benign lesions.
Wednesday, May 11, 2016
A Mechanistic Tool for Studying Fungal Pathogens
This study presents an overview of lipid extraction, chromatographic separation and mass spectrometry employed in qualitative and quantitative sphingolipidomics in fungi.
Wednesday, May 11, 2016
Acetaldehyde and Formaldehyde Content in Foods
Korean researchers have determined the content of the toxic and carcinogenic aldehydes, acetaldehyde and formaldehyde, in a variety of food groups.
Monday, November 09, 2015
Sample & Analysis Tracking in Oncogenomic Experiments
The study outlines Onco-STS, a web-based laboratory information management system for sample and analysis tracking in oncogenomic experiments.
Friday, May 08, 2015
Arabidopsis TOE Proteins Involved in the Regulation of Flowering Time
This study found that TOE proteins serve as major integrator of developmental and environmental signaling pathways, especially the photoperiod flowering pathway, triggering flowering at an appropriate age and time.
Wednesday, May 06, 2015
Aflatoxin Biosynthesis - a Novel Source of Reactive Oxygen Species
Researchers at the Michigan State University found that the aflatoxin biosynthetic pathway in A. Parasiticus directly or indirectly generates ROS in aflatoxisomes/endosomes and that Superoxide represents a significant fraction of the aflatoxin biosynthesis-derived ROS pool.
Wednesday, May 06, 2015
SSR Markers and Genetic Diversity in White Birch
The results of this study indicate that the white birch trees sampled from six geographical locations had low to moderate similarity (0.025–0.610) and suggested that the SSR primers used in this study can effectively distinguish white birch germplasm.
Wednesday, May 06, 2015
The Genetics Behind Abdominal Pigmentation in Drosophila melanogaster
This study by researchers at the North Carolina State University provides evidence that genetic variation at a number of steps in regulatory, developmental, and transport pathways may contribute to natural variation in abdominal pigmentation.
Wednesday, May 06, 2015
Selection of Reference Genes for Quantitative RT-PCR Analysis
The expression stability of 12 commonly used reference genes was analysed.
Thursday, April 02, 2015
Scientific News
How it Works: Advanced Data Analysis Using Visualization
Visualisation of data can be used to help molecular biologists tackle the vast datasets their experiments create.
Unravelling the Role of Key Genes and DNA Methylation in Blood Cell Malignancies
Researchers from the University of Nebraska Medical Center have demonstrated the role of Dnmt3a in safeguarding normal haematopoiesis.
Salford Lung Study - The First Real World Clinical Trial
In this podcast, we learn about the Salford Lung Study and its potential to revolutionize the way we assess new drugs and treatments around the world.
Point of Care Diagnostics - A Cautious Revolution
Advances in molecular biology, coupled with the miniaturization and improved sensitivity of assays and devices in general, have enabled a new wave of point-of-care (POC) or “bedside” diagnostics.
Epigenetics and Neural Cell Death
Researchers demonstrate how deregulation of an epigenetic mechanism active in early neurogenesis phases triggers neural cell death.
Ebola-Affected Countries Receive NIH Support
The National Institutes of Health has established a new program to further research capacity to study Ebola and other epidemics.
Immunotherapy Technique Holds Promise for Curing Food Allergies
Scientists develop immunotherapy technique that almost eliminating allergic response and anaphylactic response in food-allergic mice.
Skin Patch to Treat Peanut Allergy
NIH-funded study suggests peanut protein patch is a safe and convenient method of treatment.
Molecular Origins of Dust Mite Allergy Discovered
Scientists have identified molecules of house dust mites that are targeted by the immune system of children, developing allergic rhinitis and asthma.
Scientists Uncover Why Hepatitis C Vaccine is Difficult to Make
Scientists have uncovered one reason why a successful hepatitis C vaccine continues to be elusive.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,200+ scientific videos