ArticleNature communications2026
Engineering B cells to express fully customizable antibodies with enhanced Fc functions.
Chun Huang, Atishay Mathur, Chan-Hua Chang, Xiaoli Huang, Hsu-Yu Chen, Zachary B Davis, Karla O'Dell, Elizabeth A Shuman, Raymond W Kung, Geoffrey L Rogers and 1 more
Abstract read
In one paragraphArticle in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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4 · The recordCorrections and comments
5 · Who and what moneyAuthors and funding
11 authors.
Chun HuangDepartment of Immunology and Immune Therapeutics, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
Chan-Hua ChangDepartment of Immunology and Immune Therapeutics, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
Xiaoli HuangDepartment of Immunology and Immune Therapeutics, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
Hsu-Yu ChenDepartment of Immunology and Immune Therapeutics, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
Zachary B DavisDepartment of Medicine, University of Minnesota, Minneapolis, MN, USA.
Karla O'DellDepartment of Otolaryngology-Head & Neck Surgery, University of Southern California, Los Angeles, CA, USA.
Elizabeth A ShumanDepartment of Otolaryngology-Head & Neck Surgery, University of Southern California, Los Angeles, CA, USA.
Raymond W KungDepartment of Otolaryngology-Head & Neck Surgery, University of Southern California, Los Angeles, CA, USA.
Paula M CannonDepartment of Immunology and Immune Therapeutics, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA. pcannon@usc.edu.ORCID http://orcid.org/0000-0003-0059-354X Funding
USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Fumito Ito · 1985 to 2026
$181.4MReversing Immune Dysfunction for HIV-1 EradicationUM1AI164561 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI SUMIT K CHANDA, Paula M Cannon · 2021 to 2026
$30.0MPrimate CoreU19HL156247 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CANNON, PAULA M, KIEM, HANS-PETER · 2020 to 2024
$14.6MIn vivo hematopoietic stem cell engineering for HIV cureP01HL183483 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI David T Scadden · 2025 to 2026
$11.0MIn vivo engineering of B cells for the secretion of HIV broadly neutralizing antibodiesR01AI167003 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI Adi Barzel, Paula M Cannon · 2022 to 2026
$3.5MEngineering B cells for enhanced HIV controlF30AI186662 · NIAID · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Atishay Mathur · 2024 to 2026
$164kNCI NIH HHS P30 CA014089NHLBI NIH HHS P01 HL183483NHLBI NIH HHS U19 HL156247NIAID NIH HHS F30 AI186662NIAID NIH HHS R01 AI167003NIAID NIH HHS UM1 AI164561U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) HL156247U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) AI164561U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) AI167003U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) AI186662
6 · The paper itselfAbstract
Genome editing within the constant region of the immunoglobulin Heavy chain locus (IGH) can reprogram B cells to express heavy-chain-only antibodies (HCAbs) containing custom antigen-recognition domains. HCAb-engineered cells express both surface B cell receptor (BCR) and secreted antibody isoforms and respond to antigen. Here, we extend this approach to also allow customization of the constant (Fc) domain of the Heavy chain by selecting alternate editing sites within IGH, producing HCAbs with enhanced effector functions or containing mutations to extend antibody half-life. We also introduced mutations to force obligate HCAb homodimers and prevent unwanted pairing with endogenous antibody chains. Finally, we showed that additional domains could be accommodated at the HCAb C-terminus and preferentially expressed in the secreted isoform. Together, these data demonstrate the flexibility of the HCAb editing platform to express fully customized molecules that take advantage of the properties of B cells.
Indexed as
B-LymphocytesImmunoglobulin Fc FragmentsImmunoglobulin Heavy ChainsAnimalsHEK293 CellsHumansMutationProtein EngineeringReceptors, Antigen, B-CellImmunoglobulin Fc FragmentsImmunoglobulin Heavy ChainsReceptors, Antigen, B-Cell
Identifiers
PMID42129193
PMCPMC13377122
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