CHIMERIC SWITCH RECEPTORS FOR THE CONVERSION OF IMMUNESUPPRESSIVE SIGNALS TO COSTIMULATORY SIGNALS

• Main Authors: PANOWSKI, Siler, LIN, Regina Junhui, TACHEVA-GRIGOROVA, Silvia K, SASU, Barbra Johnson, LI, Zhe, ZHANG, Yi
• Format: Patent
• Language: English
• Published: 05.09.2024
• Subjects: CHEMISTRY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PEPTIDES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

Provided herein are chimeric switch receptors (CSRs) comprising an ectodomain and/or transmembrane domain derived from an inhibitory receptor (e.g. PD1 or TGFbR2) 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). 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.