Combination of an immune checkpoint modulator and a complex comprising a cell penetrating peptide, a cargo and a TLR peptide agonist for use in medicine
Inventors
Derouazi, Madiha • BELNOUE, Elodie
Assignees
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Publication Number
US-12214048-B2
Publication Date
2025-02-04
Expiration Date
Abstract
The present invention provides a combination of an immune checkpoint modulator and a complex comprising a cell penetrating peptide, at least one antigen or antigenic epitope, and a TLR peptide agonist for use in medicine, in particular in the prevention and/or treatment of cancer. Moreover, the present invention also provides compositions, such as a pharmaceutical compositions and vaccines, which are useful in medicine, for example in the prevention and/or treatment of cancer.
Core Innovation
The invention relates to cancer/tumor epitopes in which a tumor-associated antigen and a tumor-specific antigen are distinguished, including neoantigens. It describes sources for identifying tumor epitopes, including tumor epitope databases and cancer genome sequencing, and characterizes immunological presentation contexts including MHC class I, MHC class II, and CD1.
The invention further describes antigen/epitope arrangements and designs for multi-epitopic and multi-antigenic complexes, including embodiments in which multiple epitopes are positioned consecutively. The antigen or antigenic epitope can include tumor epitope and/or pathogen epitope, and may be arranged as a multi-epitopic arrangement, with CD4+ epitopes and CD8+ epitopes provided in forms intended to be presented in the specified MHC/CD1 contexts.
The invention also relates to a cancer immunotherapy combination comprising an immune checkpoint modulator and a covalently linked complex. The complex includes a cell penetrating peptide, at least one antigen or antigenic epitope, and at least one TLR peptide agonist, including preferred TLR2 or TLR4 peptide agonists, and the complex is described as supporting antigen transport and presentation and intended uses in medicine, especially cancer.
Claims Coverage
The provided independent claims cover four related claim sets centered on an immune checkpoint modulator together with a covalently linked complex comprising a cell penetrating peptide, at least one antigen or antigenic epitope, and a TLR2 or TLR4 peptide agonist. The kit claim adds directions to treat cancer, the composition claim recites a pharmaceutical composition, and one combination claim further limits the complex to a recombinant polypeptide or recombinant protein.
Immune checkpoint modulator with covalently linked CPP–antigen–TLR2/4 complex
A combination comprising an immune checkpoint modulator and a complex that includes a cell penetrating peptide, at least one antigen or antigenic epitope, and at least one TLR2 or TLR4 peptide agonist, wherein components a)-c) are covalently linked.
Cancer-treatment kit with covalently linked CPP–antigen–TLR2/4 complex
A kit comprising an immune checkpoint modulator and a complex that includes a cell penetrating peptide, at least one antigen or antigenic epitope, and at least one TLR2 or TLR4 peptide agonist, wherein components a)-c) are covalently linked, and a package insert or label having directions to treat cancer.
Pharmaceutical composition with covalently linked CPP–antigen–TLR2/4 complex
A pharmaceutical composition comprising an immune checkpoint modulator and a complex that includes a cell penetrating peptide, at least one antigen or antigenic epitope, and at least one TLR2 or TLR4 peptide agonist, wherein components a)-c) are covalently linked.
Recombinant CPP–antigen–TLR2/4 covalently linked complex for combination
A combination comprising an immune checkpoint modulator and a complex that includes a cell penetrating peptide, at least one antigen or antigenic epitope, and at least one TLR2 or TLR4 peptide agonist, wherein components a)-c) are covalently linked, and wherein the complex is a recombinant polypeptide or a recombinant protein.
Overall, the claims cover the same core concept as a combination, a kit with cancer-treatment labeling, a pharmaceutical composition, and a recombinant polypeptide or recombinant protein form of the covalently linked CPP–antigen–TLR2/4 complex. The claims are centered on the immune checkpoint modulator and the linked complex, with the kit and composition formats adding use context.
Stated Advantages
Synergy is described between PD-1/CTLA-4 blockade and specific covalently fused fusion constructs.
Improving anti-tumor activity.
Improved immune homing and increased cytokine production are described in the in vivo examples.
Therapeutic effects are described in terms of tumor growth control, improved survival, and reduced metastasis in the in vivo examples.
Enabling better responses to checkpoint blockade.
Simultaneously stimulating multi-epitopic CTL and Th responses.
Promoting immunological memory.
Documented Applications
Cancer treatment using combinations and compositions comprising an immune checkpoint modulator and a covalently linked complex containing a cell penetrating peptide, antigen or antigenic epitope, and a TLR2 or TLR4 peptide agonist.
In vivo tumor model evaluation is described using tumor growth and survival readouts and immune homing and cytokine production readouts.
Use in a kit format with a package insert or label providing directions to treat cancer is described.
Cancer treatment.
Treatment of cancer using a kit including a package insert or label having directions to treat cancer.
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