公开(公告)号：US20240216430A1

公开(公告)日：2024-07-04

申请号：US18521196

申请日：2023-11-28

Applicant: ALLOGENE THERAPEUTICS, INC. ,  PFIZER INC.

Inventor： Zhe LI ,  Siler PANOWSKI ,  Barbra Johnson SASU ,  Bryan A. SMITH ,  Thomas John VAN BLARCOM ,  Tao SAI ,  Guoyun ZHU

IPC: A61K35/17 ,  A61K39/00 ,  C07K16/28

CPC classification number: A61K35/17 ,  A61K39/4611 ,  A61K39/4631 ,  A61K39/464438 ,  C07K16/2875 ,  A61K2039/505 ,  A61K2239/13 ,  A61K2239/17 ,  A61K2239/21 ,  A61K2239/22 ,  A61K2239/23 ,  A61K2239/29 ,  A61K2239/31 ,  C07K2317/31 ,  C07K2317/565 ,  C07K2317/622

Abstract: Provided herein are Claudin 18.2 binding agents and chimeric antigen receptors (CARs) comprising a Claudin 18.2 binding molecule that specifically binds to Claudin 18.2; and immune cells comprising these Claudin 18.2-specific CARs, e.g., CAR-T cells. Also provided are methods of making and using Claudin 18.2-specific CARs and Claudin 18.2 binding agents, and immune cells comprising Claudin 18.2-specific CARs.

公开(公告)号：US20220227832A1

公开(公告)日：2022-07-21

申请号：US17557654

申请日：2021-12-21

Applicant: ALLOGENE THERAPEUTICS, INC. ,  PFIZER INC.

Inventor： Shanshan LANG ,  Thomas John VAN BLARCOM ,  Michael Thomas BETHUNE ,  Siler PANOWSKI ,  Nguyen TAN ,  Yi ZHANG ,  Barbra Johnson SASU ,  Zhe LI

IPC: C07K14/725 ,  C07K14/705 ,  C12N15/79 ,  C07K19/00

Abstract: A reversibly gated effector polypeptide e.g. a chimeric antigen receptor (protease-activating CD45-gate CAR) comprising an extracellular CD45 recruiting domain, a protease-cleavable linker, and a polypeptide comprising an extracellular ligand binding domain, a transmembrane domain, and an intracellular domain. Nucleic acids including vectors and expression vectors that encode the protease-activating CD45-gate CAR and cells including immune cells such as T cells that comprise and express the nucleic acids. Methods of treatment of various conditions including various forms of cancer comprising administering the cells including CAR T cell therapy. In some embodiments, the CD45 gate at least partially inhibits activation of the protease-activating CD45-gate CAR when the protease-activating CD45-gate CAR binds antigen. The inhibition is at least partially diminished, relieved and/or eliminated when the protease-activating CD45-gate CAR is exposed to a protease that can cleave the linker.

公开(公告)号：US20230346934A1

公开(公告)日：2023-11-02

申请号：US18191955

申请日：2023-03-29

Applicant: Allogene Therapeutics, Inc.

Inventor： Yi ZHANG ,  Silvia K. TACHEVA-GRIGOROVA ,  Barbra Johnson SASU ,  Siler PANOWSKI ,  Regina Junhui LIN ,  Zhe LI

IPC: A61K39/00 ,  C07K14/705 ,  C07K14/71 ,  C07K16/28 ,  C07K16/22 ,  C07K14/725 ,  A61P35/00

CPC classification number: A61K39/4611 ,  C07K14/70521 ,  C07K14/71 ,  C07K16/2827 ,  C07K16/22 ,  C07K14/70507 ,  C07K14/70517 ,  C07K14/7051 ,  A61K39/4631 ,  A61K39/4643 ,  A61P35/00 ,  C07K2319/03 ,  C07K2317/622 ,  C07K2319/02 ,  A61K2239/13 ,  A61K2239/21 ,  A61K2239/22 ,  A61K2239/23 ,  A61K2239/28

Abstract: Provided herein are chimeric switch receptors (CSRs) comprising an ectodomain and/or transmembrane domain derived from an inhibitory receptor (e.g. PD1 or TGFβR2) fused to the transmembrane domain and/or intracellular signaling domain derived from one or more costimulatory proteins (e.g. CD2, CD28, MyD88, DAP10 or ICOS), or variants thereof. The chimeric switch receptors are designed to convert a signal e.g. an inhibitory signal such as an immunosuppressive signal in the form of PD-L1 or TGFβ into a costimulatory signal. Also provided are engineered immune cells engineered to functionally express a chimeric switch receptor and/or a CAR and optionally also a chimeric cytokine receptor (CCR), and populations thereof, methods of making and using the engineered cells, compositions and kits comprising them, and methods of treating e.g. cancer (e.g. solid or hematologic tumors) by administering the cells and the compositions.