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    Las bacterias de ingeniería administran quimioinmunoterapia directamente a los tumores. Esta novedosa plataforma convierte un profármaco en un fármaco contra el cáncer y potencia el sistema inmunitario, mostrando potentes efectos antitumorales.

    Palabras clave:
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    Área de la Ciencia:

    • Oncología
    • Microbiología
    • Inmunología

    Sus antecedentes:

    • La quimioinmunoterapia se enfrenta a desafíos en la administración específica del tumor y la activación sostenida de agentes.
    • El desarrollo de estrategias terapéuticas integradas es crucial para un tratamiento eficaz del cáncer.

    Objetivo del estudio:

    • Ingeniería de una plataforma bacteriana que combina quimioterapia de enzimas/profármacos con inmunoterapia para mejorar el tratamiento del cáncer.
    • Evaluar la eficacia y los mecanismos de este sistema bacteriano integrado en un modelo murino de tumor sólido.

    Principales métodos:

    • Ingeniería de *E. coli* Nissle 1917 para expresar citosina deaminasa para la conversión de 5-fluorocitosina en 5-fluorouracilo.
    • Incorporación de la producción de un superagonista de IL-15 y un nanobody bloqueador de PD-L1 dentro de la plataforma bacteriana.
    • Evaluación de los efectos antitumorales y la activación de las células inmunitarias en el modelo de tumor sólido MC38.

    Principales resultados:

    • La plataforma bacteriana demostró una potente actividad antitumoral en modelos preclínicos.
    • Los estudios mecanísticos revelaron una mayor activación de las células presentadoras de antígenos, las células T y las células NK.
    • La terapia redujo eficazmente las poblaciones de células inmunosupresoras dentro del microambiente tumoral.

    Conclusiones:

    • El sistema bacteriano integrado combina con éxito la quimioterapia de enzimas/profármacos y la inmunoterapia.
    • Este enfoque supera las limitaciones de las terapias convencionales, ofreciendo una estrategia escalable y precisa para el tratamiento sinérgico del cáncer.
    • La plataforma de ingeniería presenta un perfil de seguridad mejorado para la terapia contra el cáncer.