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1. (WO2018178007) METHODS AND PHARMACEUTICAL COMPOSITIONS FOR INHIBITING T CELL PROLIFERATION IN A SUBJECT IN NEED THEREOF

Pub. No.:    WO/2018/178007    International Application No.:    PCT/EP2018/057634
Publication Date: Fri Oct 05 01:59:59 CEST 2018 International Filing Date: Tue Mar 27 01:59:59 CEST 2018
IPC: A61K 31/00
A61P 37/00
A61K 35/02
Applicants: INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE)
FONDATION IMAGINE
UNIVERSITÉ PARIS DESCARTES
ASSISTANCE PUBLIQUE-HÔPITAUX DE PARIS (APHP)
Inventors: LATOUR, Sylvain
FISCHER, Alain
WINTER, Sarah
Title: METHODS AND PHARMACEUTICAL COMPOSITIONS FOR INHIBITING T CELL PROLIFERATION IN A SUBJECT IN NEED THEREOF
Abstract:
The inventors report two siblings presenting recurrent EBV infection and Hodgkin lymphoma caused by a homozygous loss-of-function mutation in RASGRPl, a T-cell specific nucleotide exchange factor (GEF) known to activate the RAS-induced MAPK/ERK kinases pathway. In response to TCR stimulation, RASGRP 1 -deficient T cells exhibited defective ERK kinases activation and impaired proliferation that was restored by expression of wild-type RASGRPl. Thus, these results identify a novel primary immunodeficiency that highlights T- cell proliferation and offers the opportunity to develop RASGRPl inhibitor for inhibiting T cell proliferation in a subject in need thereof.