Related Experiment Video

Updated: Mar 17, 2026

Genetic Encoding of a Non-Canonical Amino Acid for the Generation of Antibody-Drug Conjugates Through a Fast Bioorthogonal Reaction
11:02

Genetic Encoding of a Non-Canonical Amino Acid for the Generation of Antibody-Drug Conjugates Through a Fast Bioorthogonal Reaction

Published on: September 14, 2018

8.3K

Extracellular Antibody Drug Conjugates Exploiting the Proximity of Two Proteins

David J Marshall1, Scott S Harried1, John L Murphy1

  • 1Centrose, Madison, Wisconsin, USA.

Molecular Therapy : the Journal of the American Society of Gene Therapy
|July 20, 2016
PubMed

Insights

New precision cancer therapy uses extracellular drug conjugates (EDCs) to target the Na+/K+-ATPase (NKA) on cancer cells. This approach achieves high selectivity and potency, offering a novel framework for cancer treatment.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Oncology

Background:

  • The Na+/K+-ATPase (NKA) is crucial for maintaining cellular resting potential.
  • NKA inhibition causes cell swelling and death, indicating its vital role.
  • Cancer cells exhibit NKA in proximity to cancer-related proteins.

Purpose of the Study:

  • To investigate targeting the NKA on cancer cells with a novel precision therapy.
  • To develop and characterize extracellular drug conjugates (EDCs) for cancer treatment.
  • To establish a framework for a new class of targeted cancer therapies.

Main Methods:

  • Covalent attachment of a small molecule NKA inhibitor to antibodies targeting cancer cell surface proteins (CD20, CD38, CD56, CD147, dysadherin).
  • Creation and testing of selective extracellular drug conjugates (EDCs).
  • Evaluation of EDC efficacy, including EC50 values and signal-to-noise ratios.

Main Results:

  • EDCs demonstrated low to mid-picomolar EC50 values and high signal-to-noise ratios (>1,000:1).
  • EDC efficacy was dependent on NKA and target protein expression on cancer cells.
  • Developed potent and selective EDCs that induce extracellular cancer cell death via necrosis-like mechanisms.

Conclusions:

  • The NKA can be effectively targeted on cancer cells using antibody-drug conjugates.
  • EDCs represent a promising new strategy for precision cancer therapy.
  • This framework enables the development of highly selective therapies targeting extracellular disease-related proteins.

More Related Videos

Chemical Conjugation of a Purified DEC-205-Directed Antibody with Full-Length Protein for Targeting Mouse Dendritic Cells In Vitro and In Vivo10:35

Chemical Conjugation of a Purified DEC-205-Directed Antibody with Full-Length Protein for Targeting Mouse Dendritic Cells In Vitro and In Vivo

Published on: February 5, 2021

4.1K
Initial Evaluation of Antibody-conjugates Modified with Viral-derived Peptides for Increasing Cellular Accumulation and Improving Tumor Targeting11:58

Initial Evaluation of Antibody-conjugates Modified with Viral-derived Peptides for Increasing Cellular Accumulation and Improving Tumor Targeting

Published on: March 8, 2018

8.1K

Related Concept Videos

Antibody Actions01:26

Antibody Actions

Antibodies, or immunoglobulins, are critical players in the immune system's arsenal against invading pathogens. Produced by B cells and plasma cells, their primary role is to detect and bind to specific antigens, molecules found on the surface of pathogens like bacteria or viruses. Beyond antigen recognition, antibodies perform several vital functions that contribute to immune defense.
Neutralization
Antibodies can bind to pathogens, preventing them from infecting host cells. This process...
3.4K
Conjugated Proteins02:50

Conjugated Proteins

Simple proteins and protein complexes contain only amino acids. In contrast, many other proteins, called conjugated proteins, covalently bond with non-protein moieties.
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
29.6K
Affinity and Avidity01:41

Affinity and Avidity

Overview
40.0K
Drug Distribution: Plasma Protein Binding01:29

Drug Distribution: Plasma Protein Binding

Drugs predominantly attach to plasma proteins, with only a small percentage remaining unbound. The unbound portion can be calculated as one minus the bound fraction. Acidic drugs form large, inactive complexes by reversibly binding to plasma albumin, which prevents them from diffusing across biological barriers. These drug-protein complexes act as reservoirs for the drugs. As the concentration of unbound drugs decreases, these complexes quickly dissociate to release the free drug, maintaining...
11.4K
Immunoprecipitation01:20

Immunoprecipitation

Immunoprecipitation, or IP, is a widely used technique that employs protein-antibody interactions to isolate proteins or protein complexes in their native state for studying protein-protein interactions, quaternary structures, or supramolecular complexes. Various modifications of the technique, including chromatin IP, cross-linking IP, and fluorescence IP, are commonly used.
Chromatin Immunoprecipitation
Chromatin immunoprecipitation, also known as ChIP, is used to study protein-DNA or...
7.8K
Antibody Structure01:10

Antibody Structure

Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
67.1K