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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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Detalles Bibliográficos
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
Descripción
Sumario: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.