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US 2026/0265375 A1Published application
Inhibitory chimeric receptor architectures
AssigneesSenti Biosciences, Inc., Trustees of Boston University
InventorsWilson Wong, Seunghee Lee, Russell Morrison Gordley, Marcela Guzman Ayala, Gary Lee, Nicholas Frankel, Xi Kang
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Abstract
Provided herein are inhibitory chimeric antigen receptor compositions and cells comprising such compositions. Also provided are methods of using inhibitory chimeric antigen receptors and cells.
Claims20
A chimeric inhibitory receptor comprising:
- (a) an extracellular protein binding domain,
- (b) a transmembrane domain, wherein the transmembrane domain is operably linked to the extracellular protein binding domain, wherein the transmembrane domain is selected from the group consisting of BTLA, CD8, CD3zeta, CD4, 4-IBB, OX40, ICOS, 2B4, CD25, CD7, LAX, LAT, PD-1, CTLA4, TIM3, KIR3DL1, LIR1, NKG2A, TIGIT, and LAG3,
- (c) one or more intracellular signaling domains, wherein the one or more intracellular signaling domains are operably linked to the transmembrane domain;
- wherein each of the one or more intracellular signaling domains is derived from a protein selected from the group consisting of BTLA, PD-1, CTLA4, TIM3, KIR3DL1, LIR1, NKG2A, TIGIT, and LAG3;
- and
- wherein at least one of the one or more intracellular signaling domains is capable of preventing, attenuating, or inhibiting activation of a tumor-targeting chimeric receptor expressed on an immunomodulatory cell.
3 more elements
A method of preventing, attenuating, or inhibiting a cell-mediated immune response of an immunomodulatory cell, comprising:
- engineering the immunomodulatory cell to express a chimeric inhibitory receptor on the surface of the immunomodulatory cell,
- wherein upon binding of a cognate protein to the chimeric inhibitory receptor, the intracellular signaling domain prevents, attenuates, or inhibits activation of the cell-mediated immune response of the immunomodulatory cell,
- wherein the chimeric inhibitory receptor comprises:
- (a) an extracellular protein binding domain,
- (b) a transmembrane domain, wherein the transmembrane domain is operably linked to the extracellular protein binding domain, wherein the transmembrane domain is selected from the group consisting of BTLA, CD8, CD3zeta, CD4, 4-IBB, OX40, ICOS, 2B4, CD25, CD7, LAX, LAT, PD-1, CTLA4, TIM3, KIR3DL1, LIR1, NKG2A, TIGIT, and LAG3,
- (c) one or more intracellular signaling domains, wherein the one or more intracellular signaling domains are operably linked to the transmembrane domain;
- and
- wherein each of the one or more intracellular signaling domains is derived from a protein selected from the group consisting of BTLA, PD-1, CTLA4, TIM3, KIR3DL1, LIR1, NKG2A, TIGIT, and LAG3.
5 more elements
A chimeric inhibitory receptor comprising:
- (a) an extracellular protein binding domain,
- (b) a transmembrane domain, wherein the transmembrane domain is operably linked to the extracellular protein binding domain, wherein the transmembrane domain is selected from the group consisting of BTLA, PD-1, CTLA4, TIM3, KIR3DL1, LIR1, NKG2A, TIGIT, and LAG3, and
- (c) one or more intracellular signaling domains, wherein the one or more intracellular signaling domains are operably linked to the transmembrane domain, and wherein the transmembrane domain and one of the one or more intracellular signaling domains are derived from the same protein;
- and
- wherein at least one of the one or more intracellular signaling domains is capable of preventing, attenuating, or inhibiting activation of a tumor-targeting chimeric receptor expressed on an immunomodulatory cell, optionally wherein the transmembrane domain further comprises at least a portion of an extracellular domain of the same protein.
2 more elements
Dependencies are inferred from the claim text.