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-12285443-B2
Publication Date
2025-04-29
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 based on specific tumor-associated HLA/HLA-variant peptide sequences, including peptides defined by SEQ ID NO: 1-216 and variant peptides, that retain MHC binding and can induce cross-reactive T cells. The disclosed peptides include extensive scope over peptide variants, including conservative substitutions and anchor-site modifications, and encompass peptide lengths and elongations for MHC class I and MHC class II contexts.
The cancer immunotherapy embodiments include vaccine and medicament use of the disclosed peptides, including pharmaceutical compositions and formulations. The disclosure also includes nucleic acids and expression vectors encoding the peptides, antibodies recognizing peptide-MHC complexes, and soluble or engineered T cell receptors recognizing peptide-MHC complexes.
Engineered antigen-presenting cells, including dendritic cells, and activated T lymphocytes are disclosed as enabling target recognition and cancer cell killing. The document reports evidence of natural peptide presentation and over-presentation in primary tumors using MS-based identification/quantitation via the XPRESIDENT® pipeline, and describes multiple cancer indications.
The invention further relates to producing and identifying antigen-binding proteins, including human antibodies, antibody fragments, and antibody libraries, by display technologies such as phage display, ribosome display, yeast display, bacterial display, baculovirus display, mammal cell display, and mRNA display. It also provides methods and compositions for generating soluble T cell receptors, including soluble TCRs produced by phage display and engineered stabilization, and single-chain TCRs or soluble TCRs linked to functional moieties.
Claims Coverage
The provided content includes independent claim families covering specific peptide compositions and a method of treating cancer with activated T cells, for a total of two recurring inventive feature groups across the claim content.
Peptide in pharmaceutically acceptable salt form
A peptide consisting of the amino acid sequence ILMILQPQL (SEQ ID NO: 10) is provided in the form of a pharmaceutically acceptable salt.
Pegylated peptide modified with PEG
A pegylated peptide comprising the amino acid sequence ILMILQPQL (SEQ ID NO: 10), optionally as a pharmaceutically acceptable salt, and modified with PEG is provided.
Activated T cells for treating cancer presenting the ILMILQPQL peptide
A method of treating a patient who has cancer includes administering a population of activated T cells that kill cancer cells that present a peptide consisting of the amino acid sequence of ILMILQPQL (SEQ ID NO: 10), where the cancer is selected from the listed group of cancer types.
Overall, the claim coverage focuses on the specific ILMILQPQL (SEQ ID NO: 10) peptide in salt and pegylated forms, and a cancer treatment method using activated T cells that kill cancer cells presenting that peptide.
Stated Advantages
The disclosed peptides retain MHC binding and can induce cross-reactive T cells.
The document reports evidence of natural peptide presentation and over-presentation in primary tumors.
Documented Applications
Cancer immunotherapy using the disclosed peptides and associated embodiments including vaccines/medicaments, nucleic acids/expression vectors, antibodies, soluble or engineered TCRs, engineered antigen-presenting cells, and activated T lymphocytes for target killing.
Treating a patient with cancer selected from the listed group, including 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.
Formulation and administration of antibodies and antibody fragments.
Diagnostic use of labeled antibodies and pathology verification.
In vivo imaging (immunoscintiography) using labeled antibodies, including imaging modalities such as PET, CT, MRI, and fluorescence.
Generation and activation of peptide-specific CD8+ T cells using peptide-loaded MHC on TAP-deficient APCs.
Adoptive transfer of activated T cells for killing tumor cells that aberrantly express tumor-associated peptides (TUMAPs) corresponding to SEQ ID NO: 1 to SEQ ID NO: 216.
In vitro immunogenicity assessment of MHC class I TUMAPs using CD8+ T cell priming with artificial APCs.
MHC binding assays for peptide exchange-yield scoring across multiple HLA allotypes and cancer indications.
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