Pd-1 decoy variants for immunotherapy
AssigneesLudwig Institute for Cancer Research, Centre Hospitalier Universitaire Vaudois, University of Lausanne
InventorsGeorge Coukos, Melita Irving, Vincent Zoete
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Abstract
The present disclosure relates to novel PD-1 decoy variants, compositions, and methods to confer and/or increase immune responses mediated by cellular immunotherapy, such as by adoptively transferring tumor-specific genetically-modified subsets of lymphocytes.
Claims38
A programmed cell death 1 (PD-1) decoy polypeptide, comprising an amino acid sequence of a PD-1 variant, wherein the amino acid sequence has at least 80% identity to SEQ ID NO:
- 6 and comprises substitutions at least at positions T76, K78, and Q133 of SEQ ID NO:
- 6.
The PD-1 decoy polypeptide of any one of the preceding claims, wherein the substitutions comprise:
- (i) T76D or a conservative substitution of D76;
- or T76V or a conservative substitution V76;
- (ii) K78R or a conservative substitution of R78;
- or
- (iii) Q133K or a conservative substitution of K133.
The PD-1 decoy polypeptide of any one of the preceding claims, wherein the additional substitutions comprise at least one of:
- (iv) L122E or a conservative substitution of E122;
- L122F or a conservative substitution of F122;
- or L122I or a conservative substitution of I122;
- and
- (v) A132W or a conservative substitution of W132;
- A132L or a conservative substitution of L132;
- or A132Y or a conservative substitution of Y132.
The PD-1 decoy polypeptide of any one of the preceding claims, wherein the amino acid sequence comprises the substitutions at the positions at T76, K78, E122, A132, and Q133.
The PD-1 decoy polypeptide of any one of the preceding claims, wherein the amino acid sequence comprises the substitutions at the positions at T76, K78, E122, and Q133.
The PD-1 decoy polypeptide of any one of the preceding claims, further comprising a fusion partner.
The PD-1 decoy polypeptide of any one of the preceding claims, further comprising a cellular elimination tag (CET).
The PD-1 decoy polypeptide of any one of the preceding claims, comprising a detectable label.
A polynucleotide comprising a polynucleotide sequence that encodes the PD-1 decoy polypeptide of any one of the preceding claims.
The cell of any one of claims 21 to 23, wherein the cell further comprises a second polynucleotide sequence encoding at least one transgene.
Dependencies are inferred from the claim text.