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Inmunoterapia contra el cáncer basada en células T CD4 + específicas de la mutación en un paciente con cáncer
Eric Tran1, Simon Turcotte, Alena Gros
1Surgery Branch, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD 20892, USA.
Science (New York, N.Y.)
|May 10, 2014
Resumen
Este estudio muestra que las células T que se dirigen a una mutación específica del cáncer pueden reducir los tumores. El aprovechamiento de estas células T específicas de la mutación condujo a la regresión tumoral en un paciente con colangiocarcinoma metastásico.
Área de la Ciencia:
- Inmunología Inmunología.
- Oncología Oncología.
- Genética La genética.
Sus antecedentes:
- La evidencia limitada sugiere que los humanos pueden montar respuestas de células T específicas de mutación contra los cánceres epiteliales.
- Los linfocitos que se infiltran en el tumor (TIL, por sus siglas en inglés) juegan un papel crucial en la respuesta inmune al cáncer.
Objetivo del estudio:
- Investigar el potencial de las respuestas de las células T específicas de mutación en la mediación de la regresión de los cánceres epiteliales metastásicos.
- Para demostrar la eficacia de la terapia de células T adoptivas dirigidas a mutaciones específicas del tumor.
Principales métodos:
- Se utilizó la secuenciación exómica completa para identificar mutaciones en los linfocitos infiltrantes de tumores (TIL).
- Las células CD4+ T helper 1 (T(H) 1 que reconocen una mutación específica (en ERBB2IP) fueron identificadas en un paciente con colangiocarcinoma metastásico.
- Se realizó la transferencia adoptiva de células TIL y células T(H) 1 purificadas y reactivas a la mutación.
Principales resultados:
- TIL contenía células CD4+ T(H) 1 que reconocían una mutación en ERBB2IP.
- La transferencia adoptiva inicial de TIL con un 25% de células T(H) 1 específicas de la mutación resultó en una disminución de las lesiones objetivo y la estabilización de la enfermedad.
- El nuevo tratamiento con una población altamente purificada (>95%) de células T(H) 1 reactivas a la mutación condujo a una mayor regresión tumoral.
Conclusiones:
- Se puede aprovechar una respuesta de células T CD4+ contra un antígeno mutado para lograr la regresión del cáncer epitelial metastásico.
- Este estudio proporciona evidencia del potencial terapéutico de dirigirse a mutaciones específicas del cáncer con células T.
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