Neoantigen landscape supports feasibility of personalized cancer vaccine for follicular lymphoma.

ABSTRACT: Personalized cancer vaccines designed to target neoantigens represent a promising new treatment paradigm in oncology. In contrast to classical idiotype vaccines, we hypothesized that "polyvalent" vaccines could be engineered for the personalized treatment of follicular lymphoma (FL) using neoantigen discovery by combined whole-exome sequencing (WES) and RNA sequencing (RNA-seq). Fifty-eight tumor samples from 57 patients with FL underwent WES and RNA-seq. Somatic and B-cell clonotype neoantigens were predicted and filtered to identify high-quality neoantigens. B-cell clonality was determined by the alignment of B-cell receptor (BCR) CDR3 regions from RNA-seq data, grouping at the protein level, and comparison with the BCR repertoire from healthy individuals using RNA-seq data. An average of 52 somatic mutations per patient (range, 2-172) were identified, and ≥2 (median, 15) high-quality neoantigens were predicted for 56 of 58 FL samples. The predicted neoantigen peptides were composed of missense mutations (77%), indels (9%), gene fusions (3%), and BCR sequences (11%). Building off of these preclinical analyses, we initiated a pilot clinical trial using personalized neoantigen vaccination combined with PD-1 blockade in patients with relapsed or refractory FL (#NCT03121677). Synthetic long peptide vaccines targeting predicted high-quality neoantigens were successfully synthesized for and administered to all 4 patients enrolled. Initial results demonstrate feasibility, safety, and potential immunologic and clinical responses. Our study suggests that a genomics-driven personalized cancer vaccine strategy is feasible for patients with FL, and this may overcome prior challenges in the field. This trial was registered at www.ClinicalTrials.gov as #NCT03121677.

Relación entre la presión de pulso y la enfermedad cerebrovascular aterotrombótica / Relation between pulse pressure and atherothrombotic cerebrovascular disease

Introducción: la presión de pulso es un importante marcador y/o predictor de riesgo de complicaciones ateroscleróticas agudas, donde está incluida la enfermedad cerebrovascular. Objetivos: determinar la relación entre la presión de pulso y la enfermedad cerebrovascular aterotrombótica en pacientes hipertensos y no hipertensos. Métodos: estudio explicativo, analítico, caso/control. El grupo de casos fue de 226 pacientes con diagnóstico de enfermedad cerebrovascular aterotrombótica, ingresados en la Sala de Ictus del Hospital General Docente Enrique Cabrera entre 2014-2016 y el grupo control de 226 sin enfermedad cerebrovascular. Se formaron dos grupos, uno con presión de pulso 60 mmhg y otro con presión de pulso < 60 mmHg en pacientes hipertensos y no hipertensos. Resultados: la media de la edad fue de 69,65 años y el 61,45 por ciento eran masculinos; la frecuencia de hipertensión arterial fue de 70,4 por ciento y la de fumadores, 35,4 por ciento y con PP≥ 60 mmHg, 62,0 por ciento. La asociación de la presión de pulso 60 mmHg con enfermedad cerebrovascular aterotrombótica en pacientes hipertensos resultó significativa con odds-ratio 4,72, Intervalo de Confianza 95 por ciento(2,79-7,98) y en pacientes no hipertensos también resultó significativa con odds-ratio 6,86 Intervalo de Confianza 95 por ciento (3,33-14,07). El riesgo atribuible en expuestos fue de 88,6 por ciento y el riesgo atribuible en la población de 50,4 por ciento. Conclusiones: la presión de pulso se asoció de forma significativa a la enfermedad cerebrovascular aterotrombótica en pacientes hipertensos y no hipertensos(AU)

Introduction: Pulse pressure is an important marker or predictor of risk for acute atherosclerotic complications, including cerebrovascular disease. Objectives: To determine the relationship between pulse pressure and atherothrombotic cerebrovascular disease in hypertensive and nonhypertensive patients. Methods: Explanatory, analytical, case control study. The case group consisted of 226 patients diagnosed with atherothrombotic cerebrovascular disease admitted to the Ictus Room at Enrique Cabrera General Teaching Hospital between 2014 and 2016, and the control group consisted of 226 patients without cerebrovascular disease. Two groups were formed, one with a pulse pressure higher than or equal to 60 mmHg and one with a pulse pressure under 60 mmHg in hypertensive and nonhypertensive patients. Results: Mean age was 69.65 years and 61.45 percent were male. The frequency of hypertension was 70.4 percent and that of smokers was 35.4 percent, and with PP≥60 mmHg, which represented 62.0 percent. The association of pulse pressure higher than or equal to 60 mmHg with atherothrombotic cerebrovascular disease in hypertensive patients was significant with odds ratio of 4.72, and confidence interval of 95 percent (2.79-7.98), while in nonhypertensive patients it was also significant with odd ratios of 6.86, and confidence interval of 95 percent CI (3.33-14.07). The attributable risk in exposed people was 88.6 percent and the attributable risk in the population was 50.4 percent. Conclusions: Pulse pressure was significantly associated with atherothrombotic cerebrovascular disease in both hypertensive and nonhypertensive patients(AU)