Terapia CAR-T: Fundamentos moleculares, retos clínicos y nuevas perspectivas

CAR-T Therapy: Molecular Fundamentals, Clinical Challenges, and Emerging Perspectives

Publicado 2026-02-17

Graphical abstract CAR-T Therapy: molecular fundamentals, clinical challenges, and emerging perspectives
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Patiño-Escobar B. Terapia CAR-T: Fundamentos moleculares, retos clínicos y nuevas perspectivas. Rev. colomb. hematol. oncol. [Internet]. 2026 Feb. 17 [cited 2026 Feb. 17];13(1-Supl):198-223. https://doi.org/10.51643/22562915.829

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Vol. 13 Núm. 1-Supl (2026): Biología molecular tumoral: de la básica a la clínica
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Patiño-Escobar B. Terapia CAR-T: Fundamentos moleculares, retos clínicos y nuevas perspectivas. Rev. colomb. hematol. oncol. [Internet]. 2026 Feb. 17 [cited 2026 Feb. 17];13(1-Supl):198-223. https://doi.org/10.51643/22562915.829
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https://doi.org/10.51643/22562915.829
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Esta obra está bajo una licencia internacional Creative Commons Atribución-NoComercial-SinDerivadas 4.0.

Bonell Patiño-Escobar
Universidad de California en San Francisco image/svg+xml
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https://orcid.org/0000-0003-2622-4822
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Bonell Patiño-Escobar,

Medico Internista. Hematólogo. Post doctoral fellow. Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA. Multiple Myeloma Research Foundation Fellow. USA.

Introducción: la terapia con células T con receptor de antígeno quimérico (CAR-T) ha revolucionado el tratamiento de las neoplasias hematológicas, estableciendo un nuevo estándar de atención en la inmunoterapia celular personalizada. No obstante, pese a su notable éxito clínico, su aplicación generalizada continúa limitada por desafíos logísticos, biológicos y de seguridad.

Métodos: en esta revisión se sintetizan los fundamentos moleculares de la biología de las células CAR-T a partir de evidencia preclínica y clínica. Se analizan los avances en el diseño de los receptores, la señalización coestimuladora y los procesos de fabricación, así como los mecanismos implicados en la resistencia terapéutica y la toxicidad.

Resultados: las mejoras iterativas en el diseño y la manufactura de CAR-T han incrementado significativamente la eficacia y la seguridad, conduciendo a múltiples aprobaciones de la FDA en leucemias de células B, linfomas y mieloma múltiple. Sin embargo, persisten limitaciones clave, incluyendo los largos tiempos de fabricación, el escape antigénico, el agotamiento de las células T, la persistencia limitada, la neurotoxicidad y la toxicidad on-target/off-tumor. Estrategias emergentes como la edición genómica, la generación de CAR-T alogénicas e in vivo, la reprogramación transcripcional y metabólica, los circuitos de biología sintética (SynNotch, SNIPR y CAR con compuertas lógicas), así como el descubrimiento de dianas conformacionales específicas y el uso de ligandos naturales, están mostrando un potencial prometedor para superar estas barreras.

Discusión: en conjunto, estos avances están transformando la terapia CAR-T en una plataforma más modular, programable y controlable, con mayor capacidad para abordar los mecanismos de resistencia y reducir la toxicidad asociada.

Conclusión: estas innovaciones anuncian una nueva era de inmunoterapias celulares más seguras y versátiles, con el potencial de expandir el impacto de la ingeniería de CAR más allá de las neoplasias hematológicas, incluyendo tumores sólidos y enfermedades inmunomediadas.

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