Antibody-drug conjugate payloads
Jan Anderl1, Heinz Faulstich, Torsten Hechler
1Heidelberg Pharma GmbH, Ladenburg, Germany.
Methods in Molecular Biology (Clifton, N.J.)
|August 6, 2013
Summary
Therapeutic antibody-drug conjugates (ADCs) rely on potent toxin payloads for cancer treatment. This review covers essential payload requirements and highlights four promising drug families used in ADCs.
Area of Science:
- Oncology
- Pharmacology
- Biotechnology
Background:
- Toxin payloads are essential for the efficacy of therapeutic antibody-drug conjugates (ADCs).
- Selecting appropriate toxic compounds is critical for successful antitumoral ADC development.
- Understanding payload characteristics is key to optimizing ADC therapy.
Purpose of the Study:
- To introduce the requirements for selecting suitable toxic payloads for antitumoral ADCs.
- To summarize the structural and mechanistic features of promising drug families for ADCs.
- To provide an overview of ADC payload development and application.
Main Methods:
- Literature review of preclinical and clinical studies on ADC payloads.
- Analysis of structural and mechanistic properties of selected drug families.
- Synthesis of requirements for effective antitumoral payloads.
Main Results:
- Identified key criteria for selecting potent and specific toxin payloads.
- Summarized four drug families with demonstrated efficacy in ADC applications.
- Highlighted structural and mechanistic insights into successful ADC payloads.
Conclusions:
- The choice of toxin payload significantly impacts ADC therapeutic potential.
- Specific structural and mechanistic features are crucial for effective antitumoral ADCs.
- Further research into novel payloads will advance ADC-based cancer therapies.
Related Concept Videos
01:26Antibody 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...
Neutralization
Antibodies can bind to pathogens, preventing them from infecting host cells. This process...
01:14Phase II Conjugation Reactions: Overview
Conjugation, a key component of phase II biotransformation reactions, is a vital process in drug detoxification. It involves transferring endogenous substances like glucuronic acid, sulfate, and glycine to drugs or their metabolites formed in phase I reactions. These conjugation reactions, often catalyzed by specific enzymes, transform potentially harmful metabolites into inactive, water-soluble forms easily excreted in urine or bile. By enhancing polarity and eliminating pharmacological...
02:50Conjugated 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...
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...
01:24Site-Targeted Drug Delivery Systems: Polymeric Carriers
Polymeric carriers enhance targeted drug delivery by increasing efficacy while minimizing off-target effects. These carriers comprise a biodegradable polymeric backbone integrated with functional elements that enable targeting, improve physicochemical properties, and regulate drug release.Targeting MechanismsThe targeting ability of polymeric carriers is mediated by a homing device, which is a molecular recognition component designed to selectively bind to specific tissues or cells. Monoclonal...
01:10Antibody 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...
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...
01:14Drug Metabolism: Phase II Reactions
Phase II reactions are essential for the detoxification and elimination of drugs from the body. These reactions involve the conjugation of parent drugs or their phase I metabolites with endogenous molecules, resulting in more hydrophilic drug conjugates. The primary conjugation reactions in this phase are sulfation and glucuronidation. Both sulfation and glucuronidation typically produce biologically inactive metabolites. However, in some cases involving prodrugs, active metabolites may be...