Compositions and methods for controlling cell signaling with chimeric receptors

A chimeric signaling receptor for controlling IL18R signaling in a cell, the chimeric signaling receptor comprising a first polypeptide and a second polypeptide, wherein:

• the first polypeptide comprises a first extracellular domain, a first transmembrane domain, and a first membrane proximal signaling domain,
• the second polypeptide comprises a second extracellular domain, a second transmembrane domain, and a second membrane proximal signaling domain,
• the first extracellular domain comprises the rapamycin binding domain of FK-binding protein 12 (FKBP) or a functional fragment thereof,
• the second extracellular domain comprises the rapamycin binding domain of FKBP12-Rapamycin Binding domain of mTOR (FRB) or functional fragment thereof;
• and wherein
• (i) the first membrane proximal signaling domain comprises an intracellular signaling domain or functional fragment of IL18R1, and the second membrane proximal signaling domain comprises an intracellular signaling domain or functional fragment of IL18RAP;
• or
• (ii) the first membrane proximal signaling domain comprises an intracellular signaling domain or functional fragment of IL18RAP, and the second membrane proximal signaling domain comprises an intracellular signaling domain or functional fragment of IL18R1.

A chimeric signaling receptor for controlling IL36R signaling in a cell, the chimeric signaling receptor comprising a first polypeptide and a second polypeptide, wherein:

• the first polypeptide comprises a first extracellular domain, a first transmembrane domain, and a first membrane proximal signaling domain,
• the second polypeptide comprises a second extracellular domain, a second transmembrane domain, and a second membrane proximal signaling domain,
• the first extracellular domain comprises the rapamycin binding domain of FK-binding protein 12 (FKBP) or a functional fragment thereof,
• the second extracellular domain comprises the rapamycin binding domain of FKBP12-Rapamycin Binding domain of mTOR (FRB) or functional fragment thereof;
• and wherein
• (i) the first membrane proximal signaling domain comprises an intracellular signaling domain or functional fragment of IL36R, and the second membrane proximal signaling domain comprises an intracellular signaling domain or functional fragment of IL1RAP;
• or
• (ii) the first membrane proximal signaling domain comprises an intracellular signaling domain or functional fragment of IL1RAP, and the second membrane proximal signaling domain comprises an intracellular signaling domain or functional fragment of IL36R.

A chimeric signaling receptor for controlling IL10R signaling in a cell, the chimeric signaling receptor comprising a first polypeptide and a second polypeptide, wherein:

• the first polypeptide comprises a first extracellular domain, a first transmembrane domain, and a first membrane proximal signaling domain,
• the second polypeptide comprises a second extracellular domain, a second transmembrane domain, and a second membrane proximal signaling domain,
• the first extracellular domain comprises the rapamycin binding domain of FK-binding protein 12 (FKBP) or a functional fragment thereof,
• the second extracellular domain comprises the rapamycin binding domain of FKBP12-Rapamycin Binding domain of mTOR (FRB) or functional fragment thereof;
• and wherein
• (i) the first membrane proximal signaling domain comprises an intracellular signaling domain or functional fragment of IL10R1, and the second membrane proximal signaling domain comprises an intracellular signaling domain or functional fragment of IL10R2;
• or
• (ii) the first membrane proximal signaling domain comprises an intracellular signaling domain or functional fragment of IL10R2, and the second membrane proximal signaling domain comprises an intracellular signaling domain or functional fragment of IL10R1.

A chimeric signaling receptor for controlling LIFR signaling in a cell, the chimeric signaling receptor comprising a first polypeptide and a second polypeptide, wherein:

• the first polypeptide comprises a first extracellular domain, a first transmembrane domain, and a first membrane proximal signaling domain,
• the second polypeptide comprises a second extracellular domain, a second transmembrane domain, and a second membrane proximal signaling domain,
• the first extracellular domain comprises the rapamycin binding domain of FK-binding protein 12 (FKBP) or a functional fragment thereof,
• the second extracellular domain comprises the rapamycin binding domain of FKBP12-Rapamycin Binding domain of mTOR (FRB) or functional fragment thereof;
• and wherein
• (i) the first membrane proximal signaling domain comprises an intracellular signaling domain or functional fragment of gp130, and the second membrane proximal signaling domain comprises an intracellular signaling domain or functional fragment of LIFrβ;
• or
• (ii) the first membrane proximal signaling domain comprises an intracellular signaling domain or functional fragment of LIFrβ, and the second membrane proximal signaling domain comprises an intracellular signaling domain or functional fragment of gp130.