Peptides and scaffolds for use in immunotherapy against head and neck squamous cell carcinoma and other cancers
Inventors
MAHR, Andrea • Weinschenk, Toni • Wiebe, Anita • SONG, Colette • Schoor, Oliver • FRITSCHE, Jens • Singh, Harpreet
Assignees
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Publication Number
US-12275776-B2
Publication Date
2025-04-15
Expiration Date
Abstract
The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.
Core Innovation
The patent describes an immunotherapy platform for cancer that uses tumor-associated T-cell peptide epitopes derived from HLA class I and optionally elongated HLA class II contexts. It focuses on peptide requirements related to MHC binding and T-cell cross-reactivity, including considerations of TCR affinity for intended immune recognition. The document provides extensive peptide sequence information, including peptides identified as SEQ ID NO: 1 to SEQ ID NO: 91, with at least one peptide explicitly specified as SLYGLGGSKRISI (SEQ ID NO: 3).
The document links selected peptides to specific cancers and indications through over-presentation and gene expression relationships, and it expands embodiments to multiple molecular and formulation formats. These embodiments include pharmaceutically acceptable salts, peptide variants and elongations, nucleic acids, expression vectors, antigen-presenting cells such as dendritic cells, vaccines, antibodies, soluble or engineered TCRs, and TCR-modified cell therapies. The platform is additionally described with HLA ligand identification considerations and quantitative population coverage for HLA-A*02 and HLA-A*24 strategies.
The disclosed strategy includes a tumor-associated peptide discovery and selection pipeline using HLA ligand identification from shock-frozen tumor tissues, label-free LC-MS relative quantitation, statistical over-presentation scoring versus normal tissues, and integration with gene expression profiling using RNASeq. It provides evidence that identified HLA-presented peptides are naturally processed and presented on primary head and neck squamous cell carcinoma samples, and it links these peptides to immunological functions including T-cell recognition and the generation of antibodies, TCRs, and soluble TCRs, in the context of therapeutic vaccination concepts.
Claims Coverage
The provided claim set centers on the isolated peptide sequence SLYGLGGSKRISI (SEQ ID NO: 3) as a pharmaceutically acceptable salt or salt form. The inventive core is supported by dependent refinements covering chloride salt identity, water and buffer in a pharmaceutical composition, production by solid-phase peptide synthesis or yeast/bacterial expression, and inclusion of selected adjuvants.
Isolated peptide as a pharmaceutically acceptable salt
An isolated peptide consisting of the amino acid sequence SLYGLGGSKRISI (SEQ ID NO: 3) in the form of a pharmaceutically acceptable salt.
Isolated peptide defined as a salt form
An isolated peptide consisting of the amino acid sequence SLYGLGGSKRISI (SEQ ID NO: 3) in the form of a salt.
Chloride salt form of the peptide
The peptide is provided in the form of a pharmaceutically acceptable salt where the salt is a chloride salt.
Pharmaceutical composition including water and buffer
A pharmaceutical composition comprising the peptide, water, and a buffer.
Peptide produced by solid-phase peptide synthesis or yeast/bacterial expression
The peptide is produced by solid-phase peptide synthesis or by expressing it in a yeast or bacterial cell system.
Pharmaceutical composition with selected immunomodulatory adjuvant list
A pharmaceutical composition that includes an adjuvant selected from a specified list of immunomodulatory agents and biologics, including anti-CD40 antibody, imiquimod/resiquimod, GM-CSF, cyclophosphamide, sunitinib, bevacizumab, interferons, CpG oligonucleotides, poly(I:C), RNA, sildenafil, PLG particulate formulations, virosomes, and multiple interleukins IL-1 through IL-23.
IL-2 as the adjuvant in the pharmaceutical composition
In the composition, the adjuvant is IL-2.
The claims are directed to the defined isolated peptide sequence SLYGLGGSKRISI (SEQ ID NO: 3) in salt form, including a pharmaceutically acceptable salt and chloride salt, with composition features such as water and buffer, production by solid-phase peptide synthesis or yeast/bacterial expression, and adjuvant-containing pharmaceutical compositions including IL-2.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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