Methods for diagnosis and treatment of proliferative...

G - Physics – 01 – N

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G01N 33/574 (2006.01) A61K 39/395 (2006.01)

Patent

CA 2608751

Methods for identifying subjects having a cancer or pre-malignant condition that will benefit from anti-CD40 therapeutic agents that modulate CD40L- mediated CD40 signaling are provided. The methods comprise the use of biomarkers of cellular apoptosis, cell proliferation and survival, and CD40 signaling pathways to monitor ex vivo response to one or more anti-CD40 therapeutic agents of interest that modulate CD40 signaling on CD40-expressing neoplastic cells. The ex vivo prognostic assays can be used alone or in conjunction with other prognostic assays to identify candidate subjects who will benefit from treatment with anti-CD40 therapeutic agents. Methods of the invention also comprise the use of these biomarkers to monitor in vivo efficacy of treatment with an anti-CD40 therapeutic agent.

La présente invention concerne des méthodes permettant d'identifier des sujets atteints d'un cancer ou présentant une pathologie précancéreuse qui vont tirer profit des agents thérapeutiques anti-CD40 lesquels modulent la signalisation CD40 médiée par CD40L. Les méthodes consistent à utiliser des biomarqueurs de l'apoptose cellulaire, de la prolifération cellulaire et de la survie cellulaire, et les mécanismes de signalisation CD40 pour surveiller ex vivo la réponse à au moins un agent thérapeutique anti-CD40 intéressant qui module la signalisation CD40 sur les cellules néoplasiques exprimant CD40. Les dosages de pronostic ex vivo peuvent être utilisés seuls ou en combinaison avec d'autres dosages de pronostic pour identifier les sujets candidats qui bénéficieront du traitement avec les agents thérapeutiques anti-CD40. Les méthodes selon l'invention comprennent également l'utilisation de ces biomarqueurs pour surveiller in vivo l'efficacité du traitement avec un agent thérapeutique anti-CD40.

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