Inducible programmed cell death-1 (pd1)-cytokine chimera for potentiated immune cell function
AssigneeSeattle Children’s Hospital d/b/a Seattle Children’s Research Institute
InventorsMichael C. Jensen, James Rosser
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Abstract
Artificial expression constructs including a PD1:cytokine chimera transgene under the control of an inducible promoter are described. The artificial expression constructs can be used to enhance the function of a recombinant receptor-immune cell (e.g., CAR-T cell). The inducible PD1:cytokine chimera transgenes disclosed herein enhance the potency of the recombinant receptor-immune cell (e.g., CAR-T cell), resulting in potentiated killing, immune cell proliferation, and/or cytokine output.
Claims159
An artificial expression construct comprising:
- an inducible promoter comprising SEQ ID NO:
- 17 and SEQ ID NO:
- 138;
- and
- a sequence encoding a programmed cell death-1 (PD1):
- cytokine chimera, wherein the PD1:
- cytokine chimera comprises a PD1 linked to a cytokine selected from:
- an interferon alpha (IFNα), an interleukin (IL)21, an IL15, an N72D mutant IL15 (IL15(N72D), an IL18, a decoy resistant IL18 (drIL18), or an IL12.
An artificial expression construct comprising a sequence encoding a programmed cell death-1 (PD1):cytokine chimera, wherein the PD1:
- cytokine chimera comprises a PD1 linked to a cytokine.
A system for potentiating immune cell function comprising:
- a first artificial expression construct encoding a PD1:cytokine chimera under the regulatory control of a first promoter, wherein the first promoter comprises a sequence having at least 95% sequence identity to any of SEQ ID NOs:
- 17-56 and a minimal promoter, and wherein the PD1:
- chimera comprises a PD1 linked to a cytokine;
- and
- a second artificial expression construct comprises a sequence encoding a recombinant receptor, the recombinant receptor comprising a binding domain that binds an antigen expressed on the surface of target cells.
A recombinant protein comprising programmed cell death-1 (PD1) and a cytokine.
Dependencies are inferred from the claim text.