Immune stimulating compositions and uses thereof
By expressing constitutively active caspase-1 with exchanged p10 and p20 domains in host cells, the innate immune system is activated, solving the problem of insufficient immune response in gene vaccines with existing adjuvants and achieving effective immune stimulation against tumors and infections.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- NYCODE THERAPEUTICS INC
- Filing Date
- 2020-04-02
- Publication Date
- 2026-04-17
AI Technical Summary
Existing adjuvants are ineffective at activating the innate immune system in gene vaccines, especially for mRNA or DNA vaccines, and lack effective pro-inflammatory cytokines and components of cytokine signaling pathways, resulting in insufficient immune responses.
Constitutively active pro-inflammatory caspases, particularly caspase-1 with exchanged p10 and p20 domains, are used to induce pyroptosis or necroptosis by expression in host cells, release damage-associated molecular patterns, activate innate immune cells, and enhance immune responses by binding to helper molecules such as immune checkpoint inhibitors and cytokines.
It significantly activates T-cell-mediated immune responses, enhances immune responses to tumors and infections, and improves the immunogenicity of vaccines, especially the immunostimulatory effect of gene vaccines.
Smart Images
Figure CN114173809B_ABST
Abstract
Claims
1. A constitutively active pro-inflammatory caspase 1 comprising exchanged p10 and p20 domains, wherein the amino acid sequence of the constitutively active pro-inflammatory caspase 1 is shown in SEQ ID NO:49 or SEQ ID NO:50 or SEQ ID NO:
51.
2. The constitutively active pro-inflammatory caspase 1 according to claim 1 is a human caspase.
3. The constitutively active pro-inflammatory caspase 1 according to claim 1 or 2, wherein the exchanged p10 and p20 domains are linked by a protease cleavable site.
4. The constitutively active pro-inflammatory caspase 1 according to claim 1 or 2, which lacks the caspase-recruitment domain.
5. The constitutively active pro-inflammatory caspase 1 according to claim 1 or 2, lacking the interdomain linkers from p20 to p10.
6. An expression construct for the constitutively active pro-inflammatory caspase 1 as described in any one of claims 1-5.
7. Use of the constitutively active pro-inflammatory caspase 1 according to any one of claims 1 to 5 or the expression construct according to claim 6 as an adjuvant for the preparation of a cancer vaccine, wherein the cancer is melanoma.
8. The use according to claim 7, wherein the caspase or expression construct is administered into the melanoma.
9. The use according to claim 7, wherein the caspase or expression construct is used as an adjuvant for systemic administration of the vaccine.
10. The use according to claim 7, wherein the caspase or expression construct is administered in combination with one or more helper molecules, wherein the helper molecules are molecules that promote T cell-mediated immune responses.
11. The use according to claim 10, wherein the T cell-mediated immune response is induced by cytotoxic T lymphocytes.
12. The use according to claim 10, wherein the one or more auxiliary molecules are immune checkpoint inhibitors, cytokines, chemokines, or combinations thereof.
13. The use according to claim 12, wherein the helper molecule is selected from: macrophage colony-stimulating factor 1; granulocyte-macrophage colony-stimulating factor CSF2; tumor necrosis factor; interferon β; interferon γ; interleukins: IL-1β, IL-2, IL-4, IL-6, IL-7, IL-8, IL-12, IL-15, IL-18, IL-21, IL-23, IL-27, IL-35; CC motif chemokine 3; CC motif chemokine 4; CC motif chemokine 20; CC motif chemokine 19; CC motif chemokine 5; CC motif chemokine 2; CC motif chemokine 8; CC motif chemokine 7; CC motif chemokine 13; CXC motif chemokine 6; platelet basal protein NAP-2; CD40 ligand; and tumor necrosis factor receptor superfamily member 4.
14. The use according to claim 10, wherein the helper molecule is selected from IL-12 and / or granulocyte-macrophage colony-stimulating factor CSF2.
15. An immunostimulatory composition comprising a constitutively active pro-inflammatory caspase 1 according to any one of claims 1 to 5 or an expression construct according to claim 6, and a pharmacologically acceptable excipient.
16. The immunostimulatory composition of claim 15, further comprising at least one antigen or a nucleic acid molecule encoded by the antigen.
17. The immunostimulatory composition according to claim 15 or 16, further comprising an auxiliary molecule.
18. The immunostimulatory composition of claim 17, wherein the helper molecule is an immune checkpoint inhibitor, a cytokine, a chemokine, or a combination thereof.
19. Use of the immunostimulatory composition of any one of claims 15 to 18 as an adjuvant in the preparation of a cancer vaccine, wherein the cancer is melanoma.
Citation Information
Patent Citations
Adjuvants that activate adaptive immune system by stimulating NLRP3
US20140037685A1
Messenger ribonucleic acids for enhancing immune responses and methods of use thereof
US20180311343A1
Hamster EF-1 alpha transcriptional regulatory DNA
US5888809A
Compositions and methods for regulating lymphocyte activation
WO1999042077A2
Nanobodies against amyloid-beta and polypeptides comprising the same for the treatment of degenerative neural diseases such as alzheimer's disease
WO2006040153A2