Peptides displayed by HLA for use in 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-12290530-B2
Publication Date
2025-05-06
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 invention relates to cancer immunotherapy and vaccine compositions and methods based on HLA/MHC-presented peptides, where the peptides are tumor-associated T cell peptide epitopes (TUMAPs) that bind specified HLA class I allotypes and induce cross-reactive T cells. The peptide embodiment includes peptides defined as SEQ ID NO: 1-216, including variants that share binding and epitope characteristics associated with the specified HLA class I allotypes.
The disclosure frames an immunological rationale for using MHC class I-presented peptide epitopes to generate T cell responses against tumors, including HLA over-presentation in tumors versus normals and confirmation of peptide identity. It further describes embodiments that include MHC class I/II binding using elongated peptides to extend coverage across related targets, including conserved anchor residue variants.
The document also describes broad immunotherapy-related embodiments for related therapeutics and diagnostics, including compositions and therapeutically relevant formats that can comprise nucleic acids, expression vectors, host/dendritic cells, activated T lymphocytes, antibodies specific to MHC-peptide complexes, soluble TCRs, and related constructs. The core subject matter is centered on the specific peptide sequence NFHTLAQQLLF (SEQ ID NO: 16) in pharmaceutically acceptable salt and PEG-modified forms and on cancer treatment by administering activated T cells that kill cancer cells presenting that peptide.
Claims Coverage
The provided claim set includes independent claims directed to the specific peptide sequence NFHTLAQQLLF (SEQ ID NO: 16) in pharmaceutically acceptable salt and salt forms, a pegylated form of that peptide, and a method of treating cancer using activated T cells that kill cancer cells presenting that peptide. Across these claims, the inventive features focus on the defined peptide sequence, PEG modification, and an activated T-cell anti-cancer mechanism directed to peptide presentation on MHC class I.
Defined peptide as pharmaceutically acceptable salt
A peptide consisting of the amino acid sequence NFHTLAQQLLF (SEQ ID NO: 16) in the form of a pharmaceutically acceptable salt.
Pegylated peptide modification of defined sequence
A pegylated peptide consisting of the amino acid sequence of NFHTLAQQLLF (SEQ ID NO: 16) or a pharmaceutically acceptable salt thereof modified with PEG.
Defined peptide provided as a salt
A peptide consisting of the amino acid sequence NFHTLAQQLLF (SEQ ID NO: 16) in the form of a salt.
Activated T-cell therapy for cancer presenting the defined peptide
A method of treating a patient who has cancer, comprising administering a population of activated T cells that kill cancer cells that present a peptide consisting of the amino acid sequence of NFHTLAQQLLF (SEQ ID NO: 16), wherein the cancer is selected from 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.
The claim coverage is centered on the specific peptide sequence NFHTLAQQLLF (SEQ ID NO: 16) in pharmaceutically acceptable salt and PEG-modified forms, and on treating cancer by administering activated T cells that kill cancer cells presenting that peptide, with claim-dependent refinements covering TCR/MHC class I recognition.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treatment of a patient who has cancer by administering an activated T-cell population that kills cancer cells presenting the peptide NFHTLAQQLLF (SEQ ID NO: 16).
Cancer indications explicitly listed in the method claim: 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.
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