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1. (WO2018009923) METHODS AND COMPOSITIONS FOR TRANSDUCING LYMPHOCYTES AND REGULATING THE ACTIVITY THEREOF

Pub. No.:    WO/2018/009923    International Application No.:    PCT/US2017/041277
Publication Date: Fri Jan 12 00:59:59 CET 2018 International Filing Date: Sun Jul 09 01:59:59 CEST 2017
IPC: C12N 15/10
C12N 15/867
C12N 5/0783
C12N 5/10
C07K 14/725
C07K 14/705
C07K 14/715
A61K 48/00
Applicants: F1 ONCOLOGY, INC.
Inventors: FROST, Gregory Ian
GUIBINGA, Ghiabe H.
ONUFFER, James Joseph
HAERIZADEH, Farzad
Title: METHODS AND COMPOSITIONS FOR TRANSDUCING LYMPHOCYTES AND REGULATING THE ACTIVITY THEREOF
Abstract:
The present disclosure provides methods for genetically modifying lymphocytes and methods for performing adoptive cellular therapy that include transducing T cells and/or NK cells. The methods can include inhibitory RNA molecule(s) and/or engineered signaling polypeptides that can include a lymphoproliferative element, and/or a chimeric antigen receptor (CAR), for example a microenvironment restricted biologic CAR (MRB-CAR). Additional elements of such engineered signaling polypeptides are provided herein, such as those that drive proliferation and regulatory elements therefor, as well as replication incompetent recombinant retroviral particles and packaging cell lines and methods of making the same. Numerous elements and methods for regulating transduced and/or genetically modified T cells and/or NK cells are provided, such as, for example, those including ribos witches, MRB-CARs, recognition domains, and/or pH-modulating agents.