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Cancer Discov ; 11(3): 560-574, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33563662

RESUMEN

Adoptive cell therapy (ACT) for cancer shows tremendous potential; however, several challenges preclude its widespread use. These include poor T-cell function in hostile tumor microenvironments, a lack of tumor-specific target antigens, and the high cost and poor scalability of cell therapy manufacturing. Creative genome-editing strategies are beginning to emerge to address each of these limitations, which has initiated the next generation of cell therapy products now entering clinical trials. CRISPR is at the forefront of this revolution, offering a simple and versatile platform for genetic engineering. This review provides a comprehensive overview of CRISPR applications that have advanced ACT. SIGNIFICANCE: The clinical impact of ACT for cancer can be expanded by implementing specific genetic modifications that enhance the potency, safety, and scalability of cellular products. Here we provide a detailed description of such genetic modifications, highlighting avenues to enhance the therapeutic efficacy and accessibility of ACT for cancer. Furthermore, we review high-throughput CRISPR genetic screens that have unveiled novel targets for cell therapy enhancement.


Asunto(s)
Sistemas CRISPR-Cas , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Edición Génica/métodos , Inmunoterapia Adoptiva/métodos , Neoplasias/terapia , Animales , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Tratamiento Basado en Trasplante de Células y Tejidos/efectos adversos , Ensayos Clínicos como Asunto , Terapia Combinada , Manejo de la Enfermedad , Evaluación Preclínica de Medicamentos , Ingeniería Genética , Terapia Genética , Humanos , Inmunoterapia Adoptiva/efectos adversos , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/inmunología , Receptores de Antígenos de Linfocitos T/metabolismo , Receptores Quiméricos de Antígenos/genética , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/metabolismo , Linfocitos T/inmunología , Linfocitos T/metabolismo , Resultado del Tratamiento
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