Combined formulation comprising four linked cytotoxic T lymphocyte (CTL) epitopes and a PD-1 pathway inhibitor and methods of use thereof to treat cancer
AssigneeTaiho Pharmaceutical Co., Ltd.
InventorYuki Tanaka
Life of this patent
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Abstract
Provided is a novel cancer treatment method that exhibits a significantly excellent antitumor effect and causes less adverse reactions. The present invention provides an antitumor agent wherein a peptide having 4 linked epitopes and an immune checkpoint modulator are administered in combination. An antitumor effect in humans can be evaluated by providing a cell coexpressing an epitope peptide of a human tumor antigen derived from SART2 and human HLA-A24.
Claims14
A combined formulation comprising a peptide having 4 linked epitopes comprising 4 CTL epitope peptides linked via linkers and a PD-1 pathway antagonist in combination,
- wherein the PD-1 pathway antagonist is at least one selected from the group consisting of an anti-PD-1 antibody, an anti-PD-L1 antibody, and an anti-PD-L2 antibody,
- wherein the peptide having 4 linked epitopes comprises:
- the epitope peptide as shown in SEQ ID NO:
- 5,
- the epitope peptide as shown in SEQ ID NO:
- 6,
- the epitope peptide as shown in SEQ ID NO:
- 9, and
- one epitope peptide selected from the group consisting of the epitope peptide as shown in SEQ ID NO:
- 2, the epitope peptide as shown in SEQ ID NO:
- 4 and the epitope peptide as shown in SEQ ID NO:
- 10, at the C terminus
- wherein the 4 linked epitopes are linked via linkers, wherein the peptide optionally further comprises a peptide sequence consisting of hydrophilic amino acids,
- wherein the linker is an arginine dimer composed of two arginine residues linked to each other,
- wherein the peptide sequence consisting of hydrophilic amino acids is linked to the N terminus and is composed of an arginine trimer composed of three arginine residues linked to each other or an arginine tetramer composed of four arginine residues linked to each other.
A method for treating a cancer in a patient by administering a peptide having 4 linked epitopes comprising 4 CTL epitope peptides linked via linkers and a PD-1 pathway antagonist,
- wherein the PD-1 pathway antagonist is at least one selected from the group consisting of an anti-PD-1 antibody, an anti-PD-L1 antibody, and an anti-PD-L2 antibody,
- wherein the peptide having 4 linked epitopes comprises:
- the epitope peptide as shown in SEQ ID NO:
- 5,
- the epitope peptide as shown in SEQ ID NO:
- 6,
- the epitope peptide as shown in SEQ ID NO:
- 9, and
- one epitope peptide selected from the group consisting of the epitope peptide as shown in SEQ ID NO:
- 2, the epitope peptide as shown in SEQ ID NO:
- 4 and the epitope peptide as shown in SEQ ID NO:
- 10, at the C terminus
- wherein the 4 linked epitopes are linked via linkers, wherein the peptide optionally further comprises a peptide sequence consisting of hydrophilic amino acids,
- wherein the linker is an arginine dimer composed of two arginine residues linked to each other,
- wherein the peptide sequence consisting of hydrophilic amino acids is linked to the N terminus and is composed of an arginine trimer composed of three arginine residues linked to each other or an arginine tetramer composed of four arginine residues linked to each other.
A method for enhancing the antitumor effect of a PD-1 pathway antagonist, comprising administering a peptide having 4 linked epitopes to a patient,
- wherein the PD-1 pathway antagonist is at least one selected from the group consisting of an anti-PD-1 antibody, an anti-PD-L1 antibody, and an anti-PD-L2 antibody,
- wherein the peptide having 4 linked epitopes comprises:
- the epitope peptide as shown in SEQ ID NO:
- 5,
- the epitope peptide as shown in SEQ ID NO:
- 6,
- the epitope peptide as shown in SEQ ID NO:
- 9, and
- one epitope peptide selected from the group consisting of the epitope peptide as shown in SEQ ID NO:
- 2, the epitope peptide as shown in SEQ ID NO:
- 4 and the epitope peptide as shown in SEQ ID NO:
- 10, at the C terminus
- wherein the 4 linked epitopes are linked via linkers, wherein the peptide optionally further comprises a peptide sequence consisting of hydrophilic amino acids,
- wherein the linker is an arginine dimer composed of two arginine residues linked to each other,
- wherein the peptide sequence consisting of hydrophilic amino acids is linked to the N terminus and is composed of an arginine trimer composed of three arginine residues linked to each other or an arginine tetramer composed of four arginine residues linked to each other.
Dependencies are inferred from the claim text.