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Contra-evolución inmune: los clones de células B inmortalizados pueden experimentar una evolución dirigida ex vivo

Casper Marsman¹, Jurgen Heinen¹, Vanessa Clerico Mosina¹

¹Kling Biotherapeutics, Amsterdam, Netherlands.

Frontiers in immunology

|September 3, 2025

Resumen

Este estudio desarrolló bibliotecas de células B inmortalizadas y dirigió la evolución para crear anticuerpos efectivos contra las variantes evolutivas del SARS-CoV-2, incluidas las cepas de escape inmunológico como JN.1.

Área de la Ciencia:

Inmunología
Virología
Biotecnología

Sus antecedentes:

La evolución del SARS-CoV-2 plantea desafíos para la vacuna y la eficacia terapéutica.
La aparición de variantes de escape inmunológico requiere el rápido desarrollo de contramedidas adaptables.

Objetivo del estudio:

Para utilizar las bibliotecas de células B inmortalizadas para identificar anticuerpos neutralizantes de reacción cruzada contra las variantes del SARS-CoV-2.
Aplicar la evolución dirigida para mejorar la potencia de unión y neutralización de anticuerpos contra las variantes emergentes del SARS-CoV-2.

Principales métodos:

Inmortalización de células B humanas de PBMC y amígdalas utilizando vectores retrovirales.
Cribado de alto rendimiento de las bibliotecas de células B para identificar clones neutralizantes.
Evolución dirigida ex vivo a través de la hipermutación somática para mejorar la afinidad de anticuerpos y la reactividad cruzada.
Ingeniería de anticuerpos biparatópicos que combinan anticuerpos neutralizantes y de unión amplia.

Principales resultados:

Se identificaron 12 clones únicos de células B con actividad de neutralización del SARS-CoV-2.
Se han desarrollado anticuerpos monoclonales con neutralización robusta contra las variantes Delta y BA.5.
La evolución dirigida aumentó la potencia de los anticuerpos contra las variantes de escape inmunológico EG.5.1 y JN.1.
El anticuerpo biparatópico modificado mostró una mayor potencia contra las variantes JN.1 y KP.3.

Conclusiones:

Las bibliotecas de células B inmortalizadas y la evolución dirigida son efectivas para desarrollar terapias contra virus en evolución.
Este enfoque ofrece una vía rápida para crear respuestas de anticuerpos adaptativos para combatir las variantes emergentes del SARS-CoV-2.

Palabras clave:

maduración por afinidad descubrimiento de anticuerpos anticuerpos biparatópicos evolución dirigida células B humanas

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