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Engineering B cells to express fully customizable antibodies with enhanced Fc functions
Chun Huang1, Atishay Mathur1, Chan-Hua Chang1
1Department of Immunology and Immune Therapeutics, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
Nature Communications
|May 13, 2026
Summary
Researchers reprogrammed B cells to create custom heavy-chain-only antibodies (HCAbs). This genome editing platform allows for enhanced effector functions, extended half-life, and tailored antibody structures for therapeutic applications.
Area of Science:
- Immunology
- Molecular Biology
- Biotechnology
Background:
- B cells naturally produce antibodies with heavy and light chains.
- Genome editing offers a way to engineer B cells for novel antibody production.
- Current methods allow customization of antigen-binding domains in heavy-chain-only antibodies (HCAbs).
Purpose of the Study:
- To extend the HCAb engineering platform to customize the antibody's constant (Fc) domain.
- To introduce mutations for enhanced effector functions and extended antibody half-life.
- To ensure HCAb homodimerization and prevent unwanted interactions with endogenous antibodies.
Main Methods:
- Utilized genome editing within the immunoglobulin Heavy chain locus (IGH).
- Selected alternate editing sites to modify the Fc domain.
- Introduced specific mutations to promote homodimerization and domain accommodation.
Main Results:
- Demonstrated the ability to engineer HCAbs with customized Fc domains.
- Achieved enhanced effector functions and extended half-life in engineered HCAbs.
- Successfully created obligate HCAb homodimers and prevented off-target pairing.
- Showcased the accommodation of additional domains at the HCAb C-terminus.
Conclusions:
- The HCAb genome editing platform is highly flexible for creating customized antibody molecules.
- Engineered HCAbs can leverage B cell properties for therapeutic potential.
- This approach enables the development of novel antibody therapeutics with tailored characteristics.
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