Células CAR-T

Células CAR-T: una nueva esperanza para el cáncer gástrico avanzado

CAR-T cells: a new hope for advanced gastric cancer

Siyuan Qian , Pedro VILLAREJO CAMPOS*,**, E. Rodríguez Cuéllar***

* Servicio de Cirugía General y del Aparato Digestivo. Hospital Universitario Fundación Jiménez Díaz.
** Departamento de Cirugía. Universidad Autónoma de Madrid.
*** Servicio de Cirugía General, Aparato Digestivo y Trasplante de Órganos Abdominales. Hospital Universitario 12 de Octubre.

DOI: https://doi.org/10.14679/4563

Resumen:

La inmunoterapia con células CAR-T está emergiendo como una alternativa prometedora para el tratamiento del cáncer gástrico avanzado, particularmente en casos de diseminación peritoneal. Esta estrategia, previamente exitosa en tumores hematológicos, se está adaptando a tumores sólidos enfrentando desafíos como la heterogeneidad tumoral y el microambiente inmunosupresor.
Diversos antígenos tumorales han sido identificados como dianas terapéuticas, entre ellos: HER2, CLDN18.2 (claudina 18.2), EpCAM y CEA. Los estudios en fase I/II muestran tasas de respuesta objetivas prometedoras con CAR-T dirigidas contra HER2 (35%) y CLDN18.2 (42%), así como potencial en otras dianas como MUC1 o EpCAM.
Una línea de investigación en expansión es la administración intraperitoneal de CAR-T, especialmente contra CEA, que ha mostrado eficacia antitumoral con baja toxicidad sistémica en modelos animales.
A pesar de estos avances, persisten retos importantes: limitada infiltración tumoral, inmunosupresión local y baja persistencia celular. Las estrategias en desarrollo incluyen CAR-T multiclonales, combinaciones con inhibidores de puntos de control, y plataformas como CAR-NK o CAR-T universales.
Conclusión: La terapia CAR-T puede convertirse en una herramienta clave en el manejo del cáncer gástrico avanzado, especialmente como parte de tratamientos multimodales. Se requieren más ensayos clínicos para validar su eficacia y seguridad en esta población.
Palabras Clave: carcinomatosis peritoneal, cáncer gástrico, inmunoterapia.

Abstract:

CAR T cell immunotherapy is emerging as a promising alternative for the treatment of advanced gastric cancer, particularly in cases of peritoneal dissemination. This strategy, previously successful in hematological tumors, is being adapted to solid tumors, addressing challenges such as tumor heterogeneity and the immunosuppressive microenvironment.
Several tumor antigens have been identified as therapeutic targets, including HER2, CLDN18.2 (claudin 18.2), EpCAM, and CEA. Phase I/II studies show promising objective response rates with CAR T cells directed against HER2 (35%) and CLDN18.2 (42%), as well as potential for other targets such as MUC1 or EpCAM.
An expanding line of research is the intraperitoneal administration of CAR T cells, especially against CEA, which has demonstrated antitumor efficacy with low systemic toxicity in animal models.
Despite these advances, significant challenges remain: limited tumor infiltration, local immunosuppression, and low cellular persistence. Strategies under development include multiclonal CAR-T cells, combinations with checkpoint inhibitors, and platforms such as CAR-NK or universal CAR-T cells.
Conclusion: CAR-T therapy can become a key tool in the management of advanced gastric cancer, especially as part of multimodality treatments. Further clinical trials are needed to validate its efficacy and safety in this population.
Key words: peritoneal carcinomatosis, gastric cancer, immunotherapy.

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