公开(公告)号：US11667691B2

公开(公告)日：2023-06-06

申请号：US15750796

申请日：2016-08-05

Applicant: Novartis AG ,  The Trustees of the University of Pennsylvania

Inventor： Andreas Loew ,  Brian Granda ,  Melissa Ramones

IPC: C07K14/725 ,  C07K16/28 ,  C07K16/30 ,  C07K19/00

CPC classification number: C07K14/7051 ,  C07K16/2803 ,  C07K16/30 ,  C07K19/00 ,  C07K2317/622 ,  C07K2317/73 ,  C07K2319/03 ,  C07K2319/70

Abstract: The present disclosure features the use of chimeric CD3 proteins to modulate T cell Receptor (TCR) signaling. Specifically, the disclosure is based, in part, on the discovery that chimeric CD3 proteins (e.g., CD3delta, CD3gamma, and CD3epsilon) having all or most of their extracellular domain fused to an antigen binding domain can activate the TCR in the presence of a cognate antigen. The disclosure is further based on the observation that the above chimeric proteins can be potentiated through the inclusion of a co-stimulatory domain in the intracellular portion of the chimeric molecule. Thus, the preferred elements of the engineered signaling complexes of the disclosure include an antigen binding domain, an extracellular domain derived from one of the above CD3 proteins, and an intracellular co-stimulatory domain.

公开(公告)号：US20190263914A1

公开(公告)日：2019-08-29

申请号：US16210480

申请日：2018-12-05

Applicant: Novartis AG ,  The Trustees of the University of Pennsylvania

Inventor： Jennifer Brogdon ,  Boris Engels ,  David Jonathan Glass ,  Brian Granda ,  John Hastewell ,  Andreas Loew ,  Joan Mannick ,  Michael C. Milone ,  Leon Murphy ,  William Raj Sellers ,  Huijuan Song ,  Brian Edward Vash ,  Jan Weiler ,  Qilong Wu ,  Li Zhou

IPC: C07K16/28 ,  A61K31/436 ,  C07K14/725 ,  C07K14/705 ,  C07K14/74 ,  C12N9/90 ,  A61K35/17 ,  C07K14/71 ,  C12N9/12

Abstract: Compositions and methods relating to regulatable chimeric antigen receptors (RCARs), where the intracellular signaling or proliferation of the RCAR can be controlled to optimize the use of an RCAR-expressing cell to provide an immune response, are provided. For example, a RCAR can comprise a dimerization switch that, upon the presence of a dimerization molecule, can couple an intracellular signaling domain to an extracellular recognition element, e.g., an antigen binding domain, an inhibitory counter ligand binding domain, or costimulatory ECD domain. An RCAR can be engineered to include an appropriate antigen binding domain that is specific to a desired antigen target and used in the treatment of a disease.