Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

BR96 conjugates of highly potent anthracyclines.

H Dalton King1, Andrew J Staab, Kahnie Pham-Kaplita

  • 1Bristol-Myers Squibb Pharmaceutical Research Institute, 06492-7660, Wallingford, CT, USA. dalton.king@bms.com

Bioorganic & Medicinal Chemistry Letters
|June 12, 2003
PubMed
Summary

New antibody-drug conjugates (ADCs) using 5-Diacetoxypentyldoxorubicin (DAPDOX) demonstrated potent, antigen-specific antitumor activity. The BR96-DAPDOX conjugate showed significant in vitro efficacy, highlighting its potential in targeted cancer therapy.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

TUB-040, a Homogeneous and Hydrophilic NaPi2b-Targeting ADC with Stably Linked Exatecan, Exhibits Long-lasting Antitumor Activity and a Well-Tolerated Safety Profile.

Molecular cancer therapeutics·2025
Same author

Mechanism-Based Enzyme Inactivation Using an Allyl Sulfoxide-Allyl Sulfenate Ester Rearrangement<sup>1</sup>.

Journal of the American Chemical Society·2024
Same author

A Multispecific Anti-CD40 DARPin Construct Induces Tumor-Selective CD40 Activation and Tumor Regression.

Cancer immunology research·2022
Same author

Chemical Modification of Linkers Provides Stable Linker-Payloads for the Generation of Antibody-Drug Conjugates.

ACS medicinal chemistry letters·2020
Same author

Experimental evidence of good efficacy and reduced toxicity with peptide-doxorubicin to treat gastric cancer.

Oncotarget·2018
Same author

Antibody drug conjugates for treatment of breast cancer: Novel targets and diverse approaches in ADC design.

Pharmacology & therapeutics·2017

Area of Science:

  • Oncology
  • Immunology
  • Medicinal Chemistry

Background:

  • Antibody-drug conjugates (ADCs) offer targeted delivery of potent cytotoxins to cancer cells.
  • Developing novel linkers and drug payloads is crucial for enhancing ADC efficacy and safety.
  • Monoclonal antibody BR96 targets tumor-associated antigens, making it a promising candidate for ADC development.

Purpose of the Study:

  • To synthesize and characterize novel 6-maleimidocaproylhydrazone derivatives of doxorubicin.
  • To conjugate these derivatives to the anti-tumor antibody BR96 and a control IgG.
  • To evaluate the in vitro potency and antigen specificity of the resulting immunoconjugates.

Main Methods:

  • Synthesis of 5-Diacetoxypentyldoxorubicin and Morpholinodoxorubicin derivatives.

Related Experiment Videos

  • Conjugation of drug derivatives to BR96 antibody and control IgG.
  • Assessment of immunoconjugate stability at different pH levels.
  • In vitro cytotoxicity assays to determine IC(50) values.

    • Main Results:

    • Successfully synthesized and conjugated doxorubicin derivatives to BR96 and IgG with controlled molar ratios and low aggregation.
    • Linkers demonstrated stability at neutral pH and drug release at acidic lysosomal pH (pH 5).
    • BR96-DAPDOX conjugate exhibited high potency and antigen specificity, with an IC(50) of 0.03 micrometer.
    • The BR96-DAPDOX conjugate was over 300-fold more potent than the non-binding IgG-DAPDOX control.

    Conclusions:

    • Novel doxorubicin derivatives conjugated to BR96 antibody form potent and antigen-specific immunoconjugates.
    • The BR96-DAPDOX conjugate shows significant promise for targeted cancer therapy due to its high in vitro efficacy.
    • The developed linker system ensures stability in circulation and targeted drug release within cancer cells.