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 Video

Updated: May 8, 2026

A GPC3-targeting Bispecific Antibody, GPC3-S-Fab, with Potent Cytotoxicity
11:13

A GPC3-targeting Bispecific Antibody, GPC3-S-Fab, with Potent Cytotoxicity

Published on: July 12, 2018

Engineered protease-resistant antibodies with selectable cell-killing functions.

Michelle Kinder1, Allison R Greenplate, Katharine D Grugan

  • 1From Biologics Research, Janssen Research and Development, LLC, Spring House, Pennsylvania 19477.

The Journal of Biological Chemistry
|August 30, 2013
PubMed
Summary
This summary is machine-generated.

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

Cellular immunology data enable clinical severity prediction via supervised machine learning.

iScience·2026
Same author

PD-1 blockade drug holiday improves exhausted progenitor CD8 T cell (Tpex) reinvigoration by avoiding Tpex adaptive resistance.

bioRxiv : the preprint server for biology·2026
Same author

Perturbation of the preterm human immune system in early life.

JCI insight·2026
Same author

Cleanet: Robust Doublet Detection in Cytometry Data Based on Protein Expression Patterns.

Cytometry. Part A : the journal of the International Society for Analytical Cytology·2025
Same author

Structure and function of therapeutic antibodies approved by the US FDA in 2024.

Antibody therapeutics·2025
Same author

Perturbation of the Preterm Human Immune System in Early Life.

medRxiv : the preprint server for health sciences·2025
Same journal

Correction: Characterization of Mast2 kinase defines structural features, regulation, and substrates.

The Journal of biological chemistry·2026
Same journal

Isotope-Edited ESEEM: A New Method for Probing Copper Binding Sites in Neurodegenerative Proteins.

The Journal of biological chemistry·2026
Same journal

Introduction to the Thematic Review Series on Intracellular Protein Degradation. The ubiquitous biology of intracellular protein degradation: a tribute to Alfred L. ("Fred") Goldberg.

The Journal of biological chemistry·2026
Same journal

Correction: Aromatic residue-rich amino-terminal segments of temporin L self-assemble into collagen-mimetic peptides with cell-adhesion properties.

The Journal of biological chemistry·2026
Same journal

YhbO is a DJ-1 family glyoxalase and α-oxoaldehyde hydratase that confers resistance to reactive carbonyl stress (112).

The Journal of biological chemistry·2026
Same journal

ARMH3 acts as a central scaffold at the Golgi/TGN through interactions with Arl5, GBF1, and PI4KB.

The Journal of biological chemistry·2026
See all related articles

Engineered antibodies resist protease cleavage, a tumor evasion tactic. Mutations in the CH2 domain restore cell-killing functions, creating a novel protease-resistant therapeutic antibody platform.

Area of Science:

  • Biotechnology
  • Immunology
  • Protein Engineering

Background:

  • Monoclonal antibody therapeutics, primarily IgG1 scaffolds, face degradation by proteases in tumor microenvironments.
  • Proteolytic cleavage in the IgG1 hinge region can abolish Fc-mediated cell-killing functions while preserving antigen binding and half-life.
  • This cleavage is a mechanism for tumors and microbes to evade host immune responses.

Purpose of the Study:

  • To engineer novel antibody scaffolds resistant to protease degradation.
  • To restore or enhance Fc-mediated cell-killing functions in protease-resistant antibodies.
  • To develop a versatile platform for protease-resistant antibody therapeutics with selective cytotoxicity.

Main Methods:

  • Engineering mutations in the CH2 domain and lower hinge region of IgG1 antibodies.
Keywords:
Antibody EngineeringImmunologyInnate ImmunityMacrophagesNK Cells

More Related Videos

Detection of Antibodies That Neutralize the Cellular Uptake of Enzyme Replacement Therapies with a Cell-based Assay
07:52

Detection of Antibodies That Neutralize the Cellular Uptake of Enzyme Replacement Therapies with a Cell-based Assay

Published on: September 10, 2018

Related Experiment Videos

Last Updated: May 8, 2026

A GPC3-targeting Bispecific Antibody, GPC3-S-Fab, with Potent Cytotoxicity
11:13

A GPC3-targeting Bispecific Antibody, GPC3-S-Fab, with Potent Cytotoxicity

Published on: July 12, 2018

Detection of Antibodies That Neutralize the Cellular Uptake of Enzyme Replacement Therapies with a Cell-based Assay
07:52

Detection of Antibodies That Neutralize the Cellular Uptake of Enzyme Replacement Therapies with a Cell-based Assay

Published on: September 10, 2018

  • Assessing protease resistance of engineered antibodies.
  • Evaluating Fc-mediated functions, including complement-dependent cytotoxicity (CDC) and Fcγ receptor (FcγR)-mediated cellular cytotoxicity.

    • Main Results:

    • Mutations in the CH2 domain, combined with lower hinge mutations, conferred protease resistance.
    • These combined mutations restored and sometimes enhanced Fc-mediated cell-killing functions.
    • The developed antibody platform demonstrated selective cell-killing capabilities while maintaining protease resistance.

    Conclusions:

    • Novel antibody engineering strategies can overcome protease-mediated evasion mechanisms.
    • The developed protease-resistant antibody platform offers a promising approach for next-generation antibody therapeutics.
    • This platform enables the design of antibodies with tailored, potent, and selective cell-killing functions for therapeutic applications.