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De la síntesis a los productos biológicos: datos preclínicos sobre una vacuna contra el cáncer derivada de la química
Jianglong Zhu1, Qian Wan, Dongjoo Lee
1Laboratory for Bioorganic Chemistry, Clinical Immunology Service, Department of Medicine, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10065, USA.
Journal of the American Chemical Society
|June 13, 2009
Resumen
Se desarrolló una nueva vacuna sintética contra el cáncer utilizando cinco antígenos de carbohidratos asociados al tumor conjugados con KLH. Estudios preclínicos en ratones demostraron su potencial para generar anticuerpos contra las células cancerosas.
Área de la Ciencia:
- Química de los hidratos de carbono.
- Inmunología Inmunología.
- Desarrollo de vacunas en desarrollo.
Sus antecedentes:
- Los cánceres de próstata y de mama expresan antígenos específicos de carbohidratos como Globo-H, GM2, STn, TF y Tn.
- El desarrollo de vacunas sintéticas dirigidas a estos antígenos es una estrategia prometedora para la inmunoterapia contra el cáncer.
Objetivo del estudio:
- Para sintetizar una vacuna contra el cáncer pentavalente totalmente sintética.
- Evaluar la inmunogenicidad y la eficacia de este nuevo candidato a vacuna en modelos preclínicos.
Principales métodos:
- Bioconjugación de un constructo pentavalente unimolecular (que contiene cinco antígenos de carbohidratos) a la hemocianina limpet de agujero de llave modificada con maleimida (KLH).
- Optimización del protocolo de conjugación para lograr una alta proporción de epítopos.
- Evaluación inmunogénica preclínica en ratones utilizando el adyuvante QS-21.
- El ensayo inmunosorbente vinculado a enzimas (ELISA) y la citometría de flujo (FACS) para la detección de anticuerpos y ensayos basados en células.
Principales resultados:
- Se preparó con éxito un conjugado sintético pentavalente de glicopéptido-KLH (vacuna 2) con una mejor relación antígeno-portador (505/1).
- ELISA confirmó la inducción de altos niveles de anticuerpos IgG e IgM contra los cinco antígenos de carbohidratos.
- El análisis FACS mostró que los anticuerpos inducidos reconocieron las células de cáncer de mama MCF-7 que expresan estos antígenos.
Conclusiones:
- La vacuna sintética pentavalente desarrollada es inmunogénica y produce anticuerpos contra los antígenos clave de carbohidratos asociados al cáncer.
- Esta vacuna candidata es prometedora para un mayor desarrollo en la inmunoterapia de la próstata y el cáncer de mama.
- Las estrategias de conjugación optimizadas son cruciales para mejorar la eficacia de la vacuna.
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