Human APOB100 epitopes, methods and uses for modulating inflammatory responses, and treating adverse cardiovascular events, disease and atherosclerosis
Inventors
Ley, Klaus • Sette, Alessandro
Assignees
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Publication Number
US-11130798-B2
Publication Date
2021-09-28
Expiration Date
Abstract
Provided herein are composition comprising novel epitopes of ApoB100, as well as sub-sequences, portions and modifications thereof, and uses thereof for treating adverse cardiovascular events, cardiovascular disease, atherosclerosis and certain liver disorders.
Core Innovation
The invention is based on ApoB100 T cell epitopes defined by short peptides having an amino acid sequence set forth in SEQ ID NOs: 2-16, 18, and 20-34, or the alternative specific sequences in SEQ ID NOs: 17 and 19, with peptide lengths described as 15-19 amino acids, including 15-17 or 15-18 ranges. These peptide sequences include ApoB100 T cell epitopes such as SLFFSAQPFEITAST (SEQ ID NO: 9) and IKHIYAISSAALSAS (SEQ ID NO: 13).
The described problem is the need to modulate immune and inflammatory responses to achieve prophylaxis, protection, or treatment of adverse cardiovascular events or cardiovascular disease, including atherosclerosis. The document also addresses liver disease, disorder, or damage in which immune modulation is used for prophylaxis, protection, or treatment.
The core concept is to use the enumerated ApoB100 T cell epitope peptides to provide immune-based outcomes such as protection and risk reduction against adverse cardiovascular events or cardiovascular disease and atherosclerosis, and to modulate responses associated with liver disease, disorder, or damage. The disclosure further includes compositions and approaches such as vaccination with adjuvants, and assessment of immune-cell binding and efficacy using MHC-II multimers.
Claims Coverage
The partial content identifies three independent claims covering short ApoB100 T cell epitope peptides, protection by administering such peptides, and treatment by administering such peptides.
Enumerated short ApoB100 T cell epitope peptides
A peptide having a length of 15-19 amino acids comprising an amino acid sequence set forth in any one of SEQ ID NOs:2-16, 18 and 20-34; a peptide having a length of 15-17 amino acids comprising an amino acid sequence set forth in SEQ ID NO:17; or a peptide having a length of 15-18 amino acids comprising an amino acid sequence set forth in SEQ ID NO:19.
Protection by administering a SEQ ID defined ApoB100 peptide
Providing a subject with protection against an adverse cardiovascular event or cardiovascular disease, atherosclerosis or liver disease, disorder or damage, comprising administering to the subject an amount of a peptide having a length of 15-19 amino acids comprising an amino acid sequence set forth in any one of SEQ ID NOs:2-34, sufficient to provide the subject with protection against the adverse cardiovascular event or cardiovascular disease, atherosclerosis or liver disease, disorder or damage.
Treating by administering a SEQ ID defined ApoB100 peptide
Treating a subject for an adverse cardiovascular event or cardiovascular disease, atherosclerosis or liver disease, disorder or damage, the method comprising administering to the subject an amount of a peptide having a length of 15-19 amino acids comprising an amino acid sequence set forth in any one of SEQ ID NOs:2-34, sufficient to treat the subject for the adverse cardiovascular event or cardiovascular disease, atherosclerosis or liver disease, disorder or damage.
Across the independent claims, the invention is centered on administering short, SEQ ID NO-defined ApoB100 T cell epitope peptides to provide protection or treat adverse cardiovascular events or cardiovascular disease, including atherosclerosis, and liver disease, disorder, or damage.
Stated Advantages
Provides protection against an adverse cardiovascular event or cardiovascular disease, including atherosclerosis.
Provides protection against liver disease, disorder or damage.
Treats a subject for an adverse cardiovascular event or cardiovascular disease, including atherosclerosis.
Treats a subject for liver disease, disorder or damage.
Documented Applications
Use of ApoB100 T cell epitope peptides for prophylaxis and protection against adverse cardiovascular events or cardiovascular disease, including atherosclerosis.
Use of ApoB100 T cell epitope peptides for treatment or risk reduction related to adverse cardiovascular events or cardiovascular disease, including atherosclerosis.
Use of ApoB100 T cell epitope peptides in connection with liver disease, disorder or damage, including outcomes associated with reduced ALT and hepatosteatosis.
Identification and assessment of ApoB-specific CD4 T cells using MHC-II multimers, including a P9 tetramer approach with peptide 18 (SEQ ID NO: 9).
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