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-12246039-B2
Publication Date
2025-03-11
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 document describes an immunotherapy platform that uses a large set of HLA (MHC) class I/II tumor-associated peptide sequences (SEQ ID NO: 1–216) together with variant peptides that retain MHC binding and can induce cross-reactive T cells. The peptides are defined as tumor-associated and are presented in peptide–MHC complexes recognized by TCR, including specific peptide sequences such as AYIPFPPLI (SEQ ID NO: 33).
The document further defines acceptable peptide variants via conservative amino acid substitutions, anchor-residue changes, and length variants, including elongated class II binders. It frames the interaction between peptide–MHC and TCR as a basis for immunogenicity and cross-reactivity, and it references peptide–MHC recognition by CD8+ T cell responses using HLA multimers.
Therapeutic and diagnostic uses are described for the peptide set and their variants, including vaccine compositions and immunotherapeutic compositions. The document also describes nucleic acids (DNA/cDNA/PNA/RNA), expression vectors, and host cells for antigen presentation, as well as antibodies and soluble TCRs specific for peptide–MHC complexes, optionally with effector or toxin functions.
Activated T lymphocytes for killing target cells and biomarker applications based on tumor-associated peptide over-presentation are also described. For identifying naturally presented HLA ligands and quantifying them across cancer and normal tissues, the document reports use of LC-MS/MS profiling and the XPRESIDENT® v2.1 pipeline.
Claims Coverage
The provided claim set includes four independent claims. The independent claim coverage centers on peptide/salt formulations, pegylated peptide modification, and a T-cell treatment method for a defined group of cancers, with peptide AYIPFPPLI (SEQ ID NO: 33) as the central target.
Pharmaceutically acceptable salt peptide AYIPFPPLI
A peptide consisting of the amino acid sequence AYIPFPPLI (SEQ ID NO: 33) in the form of a pharmaceutically acceptable salt.
PEG-modified pegylated peptide of AYIPFPPLI
A pegylated peptide consisting of the amino acid sequence of AYIPFPPLI (SEQ ID NO: 33) or a pharmaceutically acceptable salt thereof modified with PEG.
Salt form peptide AYIPFPPLI
A peptide consisting of the amino acid sequence AYIPFPPLI (SEQ ID NO: 33) in the form of a salt.
Activated T cells killing cancer cells presenting AYIPFPPLI across a defined cancer list
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 AYIPFPPLI (SEQ ID NO: 33), 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 document’s claim scope is anchored to the specific peptide AYIPFPPLI (SEQ ID NO: 33), including formulations as pharmaceutically acceptable salts and PEG-modified pegylated peptide, and a treatment method using activated T cells that kill cancer cells presenting this peptide across a defined list of cancer types.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Vaccine compositions based on the described peptide set and variants.
Use of nucleic acids/expression vectors and host cells for antigen presentation involving the described peptides.
Antibodies and soluble TCRs specific for peptide–MHC complexes, including optional effector or toxin functions.
Immunotherapeutic use with activated T lymphocytes for killing cancer cells presenting the described peptides.
Biomarker applications based on tumor over-presentation of the described peptides.
LC-MS/MS profiling and XPRESIDENT® v2.1 pipeline use to identify and quantify naturally presented HLA ligands across multiple cancer types and normal tissues.
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