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Reprogramming human B cells with custom heavy chain antibodies

We describe a genome editing strategy to reprogram the immunoglobulin heavy chain (IgH) locus of human B cells to express custom molecules that respond to immunization. These heavy chain antibodies (HCAbs) comprise a custom antigen-recognition domain linked to an Fc domain derived from the IgH locus...

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Autores principales: Rogers, Geoffrey L., Huang, Chun, Mathur, Atishay, Huang, Xiaoli, Chen, Hsu-Yu, Stanten, Kalya, Morales, Heidy, Chang, Chan-Hua, Kezirian, Eric J., Cannon, Paula M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Journal Experts 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10371167/
https://www.ncbi.nlm.nih.gov/pubmed/37503066
http://dx.doi.org/10.21203/rs.3.rs-3117686/v1
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author Rogers, Geoffrey L.
Huang, Chun
Mathur, Atishay
Huang, Xiaoli
Chen, Hsu-Yu
Stanten, Kalya
Morales, Heidy
Chang, Chan-Hua
Kezirian, Eric J.
Cannon, Paula M.
author_facet Rogers, Geoffrey L.
Huang, Chun
Mathur, Atishay
Huang, Xiaoli
Chen, Hsu-Yu
Stanten, Kalya
Morales, Heidy
Chang, Chan-Hua
Kezirian, Eric J.
Cannon, Paula M.
author_sort Rogers, Geoffrey L.
collection PubMed
description We describe a genome editing strategy to reprogram the immunoglobulin heavy chain (IgH) locus of human B cells to express custom molecules that respond to immunization. These heavy chain antibodies (HCAbs) comprise a custom antigen-recognition domain linked to an Fc domain derived from the IgH locus and can be differentially spliced to express either B cell receptor (BCR) or secreted antibody isoforms. The HCAb editing platform is highly flexible, supporting antigen-binding domains based on both antibody and non-antibody components, and also allowing alterations in the Fc domain. Using HIV Env protein as a model antigen, we show that B cells edited to express anti-Env HCAbs support the regulated expression of both BCRs and antibodies, and respond to Env antigen in a tonsil organoid model of immunization. In this way, human B cells can be reprogrammed to produce customized therapeutic molecules with the potential for in vivo amplification.
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spelling pubmed-103711672023-07-27 Reprogramming human B cells with custom heavy chain antibodies Rogers, Geoffrey L. Huang, Chun Mathur, Atishay Huang, Xiaoli Chen, Hsu-Yu Stanten, Kalya Morales, Heidy Chang, Chan-Hua Kezirian, Eric J. Cannon, Paula M. Res Sq Article We describe a genome editing strategy to reprogram the immunoglobulin heavy chain (IgH) locus of human B cells to express custom molecules that respond to immunization. These heavy chain antibodies (HCAbs) comprise a custom antigen-recognition domain linked to an Fc domain derived from the IgH locus and can be differentially spliced to express either B cell receptor (BCR) or secreted antibody isoforms. The HCAb editing platform is highly flexible, supporting antigen-binding domains based on both antibody and non-antibody components, and also allowing alterations in the Fc domain. Using HIV Env protein as a model antigen, we show that B cells edited to express anti-Env HCAbs support the regulated expression of both BCRs and antibodies, and respond to Env antigen in a tonsil organoid model of immunization. In this way, human B cells can be reprogrammed to produce customized therapeutic molecules with the potential for in vivo amplification. American Journal Experts 2023-07-17 /pmc/articles/PMC10371167/ /pubmed/37503066 http://dx.doi.org/10.21203/rs.3.rs-3117686/v1 Text en https://creativecommons.org/licenses/by/4.0/License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License (https://creativecommons.org/licenses/by/4.0/) https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Rogers, Geoffrey L.
Huang, Chun
Mathur, Atishay
Huang, Xiaoli
Chen, Hsu-Yu
Stanten, Kalya
Morales, Heidy
Chang, Chan-Hua
Kezirian, Eric J.
Cannon, Paula M.
Reprogramming human B cells with custom heavy chain antibodies
title Reprogramming human B cells with custom heavy chain antibodies
title_full Reprogramming human B cells with custom heavy chain antibodies
title_fullStr Reprogramming human B cells with custom heavy chain antibodies
title_full_unstemmed Reprogramming human B cells with custom heavy chain antibodies
title_short Reprogramming human B cells with custom heavy chain antibodies
title_sort reprogramming human b cells with custom heavy chain antibodies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10371167/
https://www.ncbi.nlm.nih.gov/pubmed/37503066
http://dx.doi.org/10.21203/rs.3.rs-3117686/v1
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