Complex comprising a cell penetrating peptide, a cargo and a TLR peptide agonist for treatment of colorectal cancer
Inventors
Derouazi, Madiha • BELNOUE, Elodie
Assignees
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Publication Number
US-12220450-B2
Publication Date
2025-02-11
Expiration Date
Abstract
The present invention provides a novel complex for use in the prevention and/or treatment of colorectal cancer, the complex comprising a) a cell penetrating peptide, b) at least one antigen or antigenic epitope, and c) at least one TLR peptide agonist, wherein the components a)-c) are covalently linked. In particular, compositions for use in the prevention and/or treatment of colorectal cancer, such as a pharmaceutical compositions and vaccines are provided.
Core Innovation
The invention relates to treating colorectal cancer or initiating, enhancing or prolonging an anti-tumor-response in a subject in need thereof by administering a complex that comprises a cell penetrating peptide, at least one antigen or antigenic epitope, and at least one toll-like receptor (TLR) peptide agonist. The at least one TLR peptide agonist is a TLR2 and/or TLR4 peptide agonist, and the components of the complex are covalently linked.
The complex is configured for use as a therapeutic vaccine and includes antigen or antigenic epitope sets related to EpCAM, MUC-1, survivin, CEA, KRas and MAGE-A3, including functional sequence variants. The antigen or antigenic epitope is presented using MHC class I and/or MHC class II presentation, including CD4+ and CD8+ epitopes, with multi-epitope and/or multi-antigen designs.
Covalent linkage between the cell penetrating peptide component, the antigen or antigenic epitope component, and the TLR agonist component is a central requirement, with optional cleavable spacers or linkers and preferred fusion-protein or recombinant formats. The document includes TLR2 and TLR4 peptide agonists and describes self-adjuvanticity and dendritic-cell targeting for the TLR peptide agonist component.
Claims Coverage
The consolidated independent claims define four treatment methods centered on a covalently linked complex that combines a cell penetrating peptide, at least one antigen or antigenic epitope, and a TLR2 and/or TLR4 peptide agonist.
Covalently linked cell penetrating peptide-antigen-TLR2/TLR4 peptide agonist complex for colorectal cancer treatment
Administering to a subject a complex comprising a cell penetrating peptide, at least one antigen or antigenic epitope, and at least one toll-like receptor (TLR) peptide agonist, wherein the TLR peptide agonist is a TLR2 and/or TLR4 peptide agonist, and wherein the components are covalently linked.
Vaccine using encoding or delivery forms for the covalently linked complex
Administering a vaccine comprising at least one of a covalently linked complex, a nucleic acid encoding the complex, a vector comprising the nucleic acid, a host cell comprising the vector, or a cell loaded with a complex.
Pharmaceutical composition containing a covalently linked complex with a pharmaceutically acceptable carrier
Administering a pharmaceutical composition comprising at least one covalently linked complex and a pharmaceutically acceptable carrier.
Combination therapy with the covalently linked complex and an additional anticancer agent
Administering a combination of the covalently linked complex and a chemotherapeutic agent, a targeted drug and/or an immunotherapeutic agent.
Across the independent claims, the core claim coverage is directed to treating colorectal cancer or initiating, enhancing or prolonging an anti-tumor-response by administering a covalently linked complex that includes a cell penetrating peptide, at least one antigen or antigenic epitope, and at least one TLR2 and/or TLR4 peptide agonist, with vaccine, pharmaceutical composition, and combination-therapy variants also claimed.
Stated Advantages
Initiates, enhances or prolongs an anti-tumor-response in a subject.
Provides self-adjuvanticity via a TLR peptide agonist.
Dendritic-cell targeting is described for the TLR peptide agonist component.
Induction of human dendritic-cell maturation markers and functional antigen presentation/cross-presentation is described in the document.
Tumor control and improved survival outcomes are described in mouse models referenced in the document.
Treats colorectal cancer.
Documented Applications
Therapeutic vaccine application for treating colorectal cancer and initiating, enhancing or prolonging an anti-tumor-response in a subject.
Vaccine delivery formats including administration of a nucleic-acid encoding the complex, a vector, a host cell, or a cell loaded with the complex.
Pharmaceutical composition use for treating colorectal cancer, comprising the covalently linked complex with a pharmaceutically acceptable carrier.
Combination therapy use with a chemotherapeutic agent, a targeted drug, and/or an immunotherapeutic agent for treating colorectal cancer and modulating an anti-tumor-response.
Use in mouse models referenced in the document, including tumor control and improved survival outcomes.
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