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Related Concept Videos

Antibody Structure01:10

Antibody Structure

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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...
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Efficient and Site-specific Antibody Labeling by Strain-promoted Azide-alkyne Cycloaddition
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Site-Specific Quadruple-Functionalised Antibodies.

Toby Journeaux1, Michael B Geeson1, Thomas V Murray2

  • 1Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.

Angewandte Chemie (International Ed. in English)
|October 18, 2024
PubMed
Summary
This summary is machine-generated.

New multi-payload antibody-drug conjugates (ADCs) overcome tumor resistance by attaching multiple functionalities to a single antibody. This breakthrough enables highly homogeneous ADCs with up to four distinct payloads for enhanced cancer therapy.

Keywords:
AntibodiesAntibody-drug conjugatesBioconjugationMultifunctionalized antibody–drug conjugatesSite-specific protein modification

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Area of Science:

  • Bioconjugation Chemistry
  • Oncology Therapeutics
  • Protein Engineering

Background:

  • Antibody-drug conjugates (ADCs) show clinical success but face limitations due to tumor heterogeneity and resistance.
  • Existing ADCs often struggle with efficacy due to these challenges.
  • Multi-payload ADCs, featuring multiple distinct payloads on a single antibody, are emerging as a solution.

Purpose of the Study:

  • To develop highly homogeneous multi-functionalized antibody conjugates with multiple distinct payloads.
  • To overcome the limitations of current ADCs in treating heterogeneous and resistant tumors.
  • To establish a new platform for next-generation ADC development.

Main Methods:

  • Utilized multiple orthogonal site-specific protein modification strategies.
  • Engineered antibody conjugates with up to four different functionalities at unique antibody sites.
  • Employed a site-specific cyclopropenone (CPO)-based reagent for payload attachment.

Main Results:

  • Successfully generated highly homogeneous multi-functionalized antibody conjugates.
  • Demonstrated the ability to install up to four distinct functionalities on a single antibody.
  • Achieved the first homogeneous multi-payload ADC with a payload count exceeding two.

Conclusions:

  • This work presents a novel approach to creating advanced multi-payload ADCs.
  • The developed methodology facilitates the creation of next-generation ADCs with enhanced therapeutic potential.
  • The homogeneous nature and high payload capacity of these conjugates offer a promising strategy against tumor resistance.