MÉTHODES DE PRODUCTION DE LYMPHOCYTES T AUTOLOGUES UTILISÉS POUR TRAITER LES TUMEURS MALIGNES À LYMPHOCYTES B ET D'AUTRES CANCERS, ET COMPOSITIONS ASSOCIÉES
FELDMAN, Steven, A.;BETTER, Marc;BETTER;ROSENBERG, Steven, A.; Marc
发明人:
BETTER, Marc,FELDMAN, Steven, A.,ROSENBERG, Steven, A.
申请号:
USUS2015/014520
公开号:
WO2015/120096A3
申请日:
2015.02.04
申请国别(地区):
US
年份:
2015
代理人:
摘要:
Provided herein are methods for manufacturing T cells. In certain embodiments, methods for manufacturing T cells which express a cell surface receptor that recognizes a specific antigenic moiety on the surface of a target cell are provided. Such methods may include, but are not limited to, steps of (1 ) enriching a population of lymphocytes obtained from a donor subject; (2) stimulating the population of lymphocytes with one or more T-cell stimulating agents to produce a population of activated T cells, wherein the stimulation is performed in a closed system using serum-free culture medium; (3) transducing the population of activated T cells with a viral vector comprising a nucleic acid molecule which encodes the cell surface receptor, using a single cycle transduction to produce a population of transduced T cells, wherein the transduction is performed in a closed system using serum-free culture medium; and (4) expanding the population of transduced T cells for a predetermined time to produce a population of engineered T cells, wherein the expansion is performed in a closed system using serum-free culture medium. Also provided herein are populations of engineered T cells produced by the methods described herein and pharmaceutical compositions thereof.L'invention concerne des méthodes de fabrication de lymphocytes T. L'invention concerne, dans certains modes de réalisation, des méthodes de fabrication des lymphocytes T qui expriment un récepteur de surface cellulaire qui reconnaît un fragment antigénique spécifique à la surface d'une cellule cible. Ces méthodes peuvent comprendre, mais sans s'y limiter, les étapes consistant à (1) enrichir une population de lymphocytes prélevés chez un sujet donneur; (2) stimuler la population de lymphocytes avec un ou plusieurs agents de manière à produire une population de lymphocytes T activés, la stimulation étant effectuée dans un système fermé à l'aide d'un milieu de culture exempt de sérum; (3) transduire la population de lymp