IP Library › Patent Application 19551160
Patent Application
App. No. 19/551,160

CHIMERIC CYTOKINE RECEPTORS BEARING A PD-1 ECTODOMAIN

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Patent No.
US None
App. No.
19/551,160
Abstract

Provided herein are PD-1 chimeric cytokine receptors. When present on chimeric antigen receptor (CAR)-bearing immune cells, such receptors allow for increased immune cell activation, proliferation, persistence, and/or potency, when engaged with PD-1 ligands or activation with an anti-PD-1 antibody. Also provided are methods of making and using the chimeric cytokine receptors described herein.

Claims (14)

1 . A PD-1 chimeric cytokine receptor comprising:

a. a PD-1 ectodomain or a PD-L1 antigen binding domain of an anti-PD-L1 or an anti-PD-L2 antibody;

b. a transmembrane domain and a Janus Kinase (JAK)-binding domain comprising SEQ ID NO: 40, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, or SEQ ID NO: 27; and

c. a STAT recruiting domain comprising a STAT-recruiting domain from a receptor selected from the group consisting of BLNK, IL2RG, EGFR, EpoR, GHR, IFNAR1, IFNAR2, IFNAR1/2, IFNLR1, IL10R1, IL12Rb1, IL12Rb2, IL21R, IL2small, IL7R, IL7Ra, IL9R, IL15R, and IL21R.

2 . The chimeric cytokine receptor of claim 1 , wherein the STAT-recruiting domain comprises the sequence selected from SEQ ID NOs: 45-55, 57-71 and 78-87.

3 . The PD-1 chimeric cytokine receptor of claim 1 , wherein the PD-1 ectodomain comprises a wild type PD-1 ectodomain sequence.

4 . The PD-1 chimeric cytokine receptor of claim 1 , wherein the PD-1 ectodomain comprises one or more mutations to the wild type PD-1 ectodomain sequence.

5 . The chimeric cytokine receptor of claim 4 , wherein the PD-1 ectodomain comprising one or more mutations has a higher binding affinity for its ligand than a wild type PD-1 ectodomain.

6 . The PD-1 chimeric cytokine receptor of claim, wherein the PD-1 ectodomain comprises an amino acid sequence selected from SEQ ID NOs: 2-5, 132-133, and 168-169.

7 . The chimeric cytokine receptor of claim 1 , wherein the PD-L1 antigen binding domain is an scFv.

8 . The chimeric cytokine receptor of claim 1 , wherein the chimeric cytokine receptor is activated when the PD-1 ectodomain is bound to PD-L1 or PD-L2.

9 . The chimeric cytokine receptor of claim 1 , wherein the chimeric cytokine receptor is activated when the PD-1 ectodomain is bound to an anti-PD-1 antibody.

10 . The chimeric cytokine receptor of claim 9 , wherein the anti-PD-1 antibody is nivolumab or pembrolizumab.

11 . The chimeric cytokine receptor of claim 1 , wherein the receptor is constitutively active and can be further induced.