Peptides displayed by HLA for use immunotherapy against different types of cancers
Inventors
Hannen, Ricarda • Hukelmann, Jens • Koehler, Florian • Kowalewski, Daniel Johannes • Schuster, Heiko • Schoor, Oliver • Roemer, Michael • Tsou, Chih-Chiang • FRITSCHE, Jens
Assignees
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Publication Number
US-12274716-B2
Publication Date
2025-04-15
Expiration Date
Abstract
The invention relates to a peptide comprising an amino acid sequence selected from the group consisting of (i) SEQ ID NO: 1 to SEQ ID NO: 216, and (ii) a variant sequence thereof which maintains capacity to bind to MHC molecule(s) and/or induce T cells cross-reacting with said variant peptide, or a pharmaceutically acceptable salt thereof.
Core Innovation
The disclosure provides cancer immunotherapy peptides derived from HLA class I tumor-associated epitopes, including variant sequences that maintain MHC binding and induce cross-reactive T cells. The peptides are defined by amino acid sequences identified in SEQ ID NO: 1-216, and related peptide characteristics are described with reference to MHC class I binding.
The document describes the peptides as forming complexes with MHC/HLA molecules, with emphasis on peptide over-presentation and cross-reactive T cell responses. In addition to HLA class I peptides, elongated MHC class II peptides are described, together with variant formats that include conservative substitutions and anchor position modifications to preserve binding characteristics.
The document further describes immunologic reagents associated with these peptide targets, including antibodies specific to MHC-peptide complexes, soluble and cloned TCRs, and engineered host cells or antigen-presenting cells presenting the peptides. The peptides and related reagents are described in the context of pharmaceutical targets and biomarker use based on over-presented HLA-peptide complexes, including diagnostic/prognostic uses and an HLA-peptidomics identification workflow supported by LC-MS evidence.
A representative peptide specifically recited in the claims is the amino acid sequence VYIASSFKI (SEQ ID NO: 3), provided as a pharmaceutically acceptable salt and also in pegylated form modified with PEG. The disclosed therapeutic approach includes administering activated T cells that kill cancer cells presenting the VYIASSFKI (SEQ ID NO: 3) peptide, with an explicit set of cancer types and optional inclusion of adjuvant or immunomodulatory agents and cytokines.
Claims Coverage
The provided claim set includes four independent claims, covering a specific peptide salt form, a pegylated version with PEG modification, a salt-form peptide itself, and a patient-treatment method using activated T cells targeting the peptide in MHC class I context across multiple cancer types. The claim coverage centers on the peptide VYIASSFKI (SEQ ID NO: 3) and its formulation as salts or PEG-modified peptide, and on T-cell killing of cancer cells that present this peptide.
Peptide in pharmaceutically acceptable salt form
A peptide consisting of the amino acid sequence VYIASSFKI (SEQ ID NO: 3) in the form of a pharmaceutically acceptable salt.
Pegylated peptide modified with PEG
A pegylated peptide consisting of the amino acid sequence of VYIASSFKI (SEQ ID NO: 3) or a pharmaceutically acceptable salt thereof modified with PEG.
Peptide in salt form
A peptide consisting of the amino acid sequence VYIASSFKI (SEQ ID NO: 3) in the form of a salt.
Activated T cells that kill cancer cells presenting the peptide
A method of treating a patient who has cancer, comprising administering to said patient a population of activated T cells that kill cancer cells that present a peptide consisting of the amino acid sequence of VYIASSFKI (SEQ ID NO: 3), wherein the cancer is selected from the group consisting of acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, gastro-esophageal junction cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, non-small cell lung cancer, ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, small cell lung cancer, urinary bladder carcinoma, and uterine endometrial cancer.
Across the independent claims, the coverage is directed to the specific HLA class I tumor-associated epitope peptide VYIASSFKI (SEQ ID NO: 3) in salt and PEG-modified forms, and to treating selected cancers by administering activated T cells that kill cancer cells presenting this peptide.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating a patient who has cancer by administering a population of activated T cells that kill cancer cells presenting the VYIASSFKI (SEQ ID NO: 3) peptide, with cancer selected from a defined group of cancer types.
Antibody-related applications for diagnostic and imaging uses of labeled antibodies, including tumor imaging and immunoscintigraphy, are described in the partial content.
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