RESUMEN
Cancer is a disease caused by DNA mutations. Cancer therapies targeting defined functional mutations have shown clinical benefit. However, as 95% of the mutations in a tumour are unique to that single patient and only a small number of mutations are shared between patients, the addressed medical need is modest. A rapidly determined patient-specific tumour mutation pattern combined with a flexible mutation-targeting drug platform could generate a mutation-targeting individualised therapy, which would benefit each single patient. Next-generation sequencing enables the rapid identification of somatic mutations in individual tumours (the mutanome). Immunoinformatics enables predictions of mutation immunogenicity. Mutation-targeting RNA-based vaccines can be rapidly and affordably synthesised as custom GMP drug products. Integration of these cutting-edge technologies into a clinically applicable process holds the promise of a disruptive innovation benefiting cancer patients. Here, we describe our translation of the individualised RNA-based cancer vaccine concept into clinic trials.
Asunto(s)
Vacunas contra el Cáncer/genética , Medicina de Precisión , ARN Neoplásico/genética , Investigación Biomédica Traslacional , Evaluación Preclínica de Medicamentos , Humanos , MutaciónRESUMEN
OBJECTIVES: Takayasu arteritis is well known as a cause of stroke in Asia but has rarely been described in the Western world. Here we report the clinical and neuroimaging follow-up of a series of patients with Takayasu arteritis from Europe. METHODS: Seventeen consecutive patients who fulfilled the diagnostic criteria for Takayasu arteritis of the American College of Rheumatology were evaluated on follow-up by standardized neurological examination, sonography and MRI. RESULTS: At follow-up almost 20 yr after onset of symptoms, the subclavian artery and the common carotid artery were often affected. In addition, evidence of intracranial pathology was found in seven patients. In contrast to the severe vessel involvement, the neurological state was stable. Two patients had suffered from stroke before the diagnosis was made and therapy was initiated, and one patient had recurrent transient ischaemic attacks. Intermittent dizziness was associated with pathology of the vertebral and basilar arteries. However, clinical symptoms of subclavian steal syndrome were rare. CONCLUSION: This case series shows that the clinical neurological course of Takayasu arteritis on treatment is benign in most cases despite the severe vascular involvement.