The General Hospital Corporation;Dana-Farber Cancer Institute, Inc.
发明人:
HACOHEN, Nir,WU, Catherine
申请号:
ES11781409
公开号:
ES2564841T3
申请日:
2011.05.16
申请国别(地区):
ES
年份:
2016
代理人:
摘要:
A method for identifying a plurality of neoantigenic peptides to prepare a specific immunogenic composition of a subject, each neoantigenic peptide comprising a tumor specific neoepitope comprising a tumor specific mutation, a method comprising: a. Identify a plurality of subject-specific tumor mutations in genes expressed from a subject who has cancer by sequencing whole genome or complete exome nucleic acids from tumor and normal tissue samples from the subject, where mutations are present in the genome of the subject's cancer cells but not in the normal tissue of the subject; b. where when a mutation identified in stage (a) is a point mutation: i. identifying a mutant peptide having the mutation identified in step (a), wherein said mutant peptide comprises a tumor-specific neoepitope that binds to a class I HLA protein with a higher affinity than a natural peptide; and having an IC50 of less than 500 nM; C. where when a mutation identified in stage (a) is a site mutation, structural change, reading or gene fusion mutation: i. identifying a mutant polypeptide encoded by the mutation identified in step (a), wherein said mutant polypeptide comprises a tumor-specific neoepitope that binds to a class I HLA protein.Un método para identificar una pluralidad de péptidos neoantigénicos para preparar una composición inmunogénica específica de un sujeto, comprendiendo cada péptido neoantigénico un neoepítopo específico de tumor que comprende una mutación específica de tumor, método que comprende: a. identificar una pluralidad de mutaciones tumorales específicas de sujeto en genes expresados de un sujeto que tenga cáncer mediante secuenciamiento de ácidos nucleicos de genoma completo o de exoma completo de muestras del tumor y de tejido normal procedentes del sujeto, donde las mutaciones están presentes en el genoma de las células cancerígenas del sujeto pero no en el tejido normal del sujeto; b. donde cuando una mutación identificada en la etapa (a) es una mutación puntual: