Live biopharmaceuticals that secrete synthetic bacteriophages in cancer treatment
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- TATUM BIOSCIENCE INC
- Filing Date
- 2026-03-06
- Publication Date
- 2026-06-09
AI Technical Summary
【0012】 様々な態様によれば、治療剤は結合タンパク質である。一部の場合には、結合タンパク質は、発がん、がんの発生、又は転移の発生に関与する1つ又は複数のタンパク質、ペプチド、又は分子に結合し、それらを阻害する。一部の他の場合には、阻害しようとする1つ又は複数のタンパク質、ペプチド、又は分子は、CSF1、CSF1R、CCR4、CCL2、CCL17、CCL22、HER2、GD2、IL-1β、IL-6、IL-10、IL-13、IL-17、IL-27、IL-35、CD20、CD27、CD30、CD33、CD70、TGF-β、M-CSF、EGFR、ERBB2、ERBB3、PGE2、VEGF、VEGFR-2、CXCR4/CXCL12、Tie2、ガレクチン-1、ガレクチン-3、ホスファチジルセリン、並びにTAM及びTimホスファチジルセリン受容体から選択される。一部の場合には、結合タンパク質は、がん性細胞の排除を導く共刺激受容体を活性化するアゴニストとして作用し、1つ又は複数の共刺激細胞受容体は、CD40、CD27、CD28、CD70、ICOS、CD357、CD226、CD137、及びCD134から選択されるが、これらに限定はされない。一部の他の場合には、結合タンパク質は、免疫チェックポイント分子、例えば、CCR4、CTLA-4、CD80、CD86、PD-1、PD-L1、PD-L2、TIGIT、VISTA、LAG-3、TIM1、TIM3、CEACAM1、LAIR-1、HVEM、BTLA、CD47、SIRPα、CD160、CD200、CD200R、CD39、CD73、B7-H3、B7-H4、IDO、TDO、KIR、及びA2aRであるが、これらに限定されないものを阻害する。
Smart Images
Figure 2026094386000007 
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Figure 2026094386000009
Abstract
Claims
1. A synthetic therapeutic bacteriophage that presents at least one therapeutic agent, wherein at least one therapeutic agent is fused with a coating protein of the synthetic bacteriophage.
2. A synthetic therapeutic bacteriophage according to claim 1, which is a filamentous bacteriophage.
3. A synthetic therapeutic bacteriophage according to claim 1 or 2, comprising a bacteriophage secretion system including a bacteriophage mechanism.
4. The synthetic therapeutic bacteriophage according to claim 3, wherein the bacteriophage mechanism includes a bacteriophage assembly module, a bacteriophage replication module, a bacteriophage coating module, and a therapeutic module.
5. The synthetic therapeutic bacteriophage according to claim 4, wherein the therapeutic module comprises at least one therapeutic agent to be presented by the synthetic therapeutic bacteriophage.
6. The synthetic therapeutic bacteriophage according to claim 5, wherein the therapeutic module comprises one or more bacteriophage coating genes selected from gpIII, gpVI, gpVII, gpVIII, and gpIX or parts thereof, each encoding or a portion thereof of the coating proteins pIII, pVI, pVII, pVIII, and pIX.
7. A synthetic therapeutic bacteriophage according to any one of claims 1 to 6, wherein at least one therapeutic agent is presented in at least a portion of the coating protein.
8. A synthetic therapeutic bacteriophage according to any one of claims 1 to 7, further presenting multiple therapeutic agents.
9. The synthetic therapeutic bacteriophage according to claim 8, wherein the second therapeutic agent is presented in at least a portion of the coating protein that does not present the first therapeutic agent.
10. A synthetic therapeutic bacteriophage according to any one of claims 3 to 9, wherein the bacteriophage mechanism further comprises a regulatory module.
11. The synthetic therapeutic bacteriophage according to claim 10, wherein the regulatory module includes a regulatory element that controls the activity of the bacteriophage mechanism.
12. The synthetic therapeutic bacteriophage according to claim 1, wherein the therapeutic agent is a binding protein.
13. The synthetic therapeutic bacteriophage according to claim 12, wherein the binding protein binds to one or more proteins, peptides, or molecules involved in carcinogenesis, cancer development, or metastasis.
14. A synthetic therapeutic bacteriophage according to claim 13, wherein one or more proteins, peptides, or molecules inhibit one or more molecules selected from CSF1, CSF1R, CCR4, CCL2, CCL17, CCL22, HER2, GD2, IL-1β, IL-6, IL-10, IL-13, IL-17, IL-27, IL-35, CD20, CD27, CD30, CD33, CD70, TGF-β, M-CSF, EGFR, ERBB2, ERBB3, PGE2, VEGF, VEGFR-2, CXCR4 / CXCL12, Tie2, galectin-1, galectin-3, phosphatidylserine, and one or more molecules selected from TAM and Tim phosphatidylserine receptors.
15. The synthetic therapeutic bacteriophage according to claim 12, wherein the binding protein acts as an agonist that activates a costimulatory receptor that leads to the elimination of cancer cells.
16. The synthetic therapeutic bacteriophage according to claim 15, wherein one or more costimulatory cell receptors are selected from CD40, CD27, CD28, CD70, ICOS, CD357, CD226, CD137, and CD134.
17. The synthetic therapeutic bacteriophage according to claim 12, wherein the binding protein inhibits an immune checkpoint molecule.
18. The synthetic therapeutic bacteriophage according to claim 17, wherein the immune checkpoint molecule is selected from CCR4, CTLA-4, CD80, CD86, PD-1, PD-L1, PD-L2, TIGIT, VISTA, LAG-3, TIM1, TIM3, CEACAM1, LAIR-1, HVEM, BTLA, CD47, SIRPα, CD160, CD200, CD200R, CD39, CD73, B7-H3, B7-H4, IDO, TDO, KIR, and A2aR.
19. The synthetic therapeutic bacteriophage according to claim 18, wherein the immune checkpoint molecule is CD47.
20. The synthetic bacteriophage according to claim 18, wherein the immune checkpoint molecule is PD-L1.
21. The synthetic bacteriophage according to claim 18, wherein the immune checkpoint molecule is CTLA-4.
22. A synthetic therapeutic bacteriophage according to claim 1, wherein the therapeutic agent stimulates an immune response.
23. The synthetic therapeutic bacteriophage according to claim 1, wherein the therapeutic agent is an antibody or an antibody mimetic.
24. A synthetic therapeutic bacteriophage according to claim 1, wherein the therapeutic agent is a nanobody.
25. A synthetic therapeutic bacteriophage according to claim 1, wherein the therapeutic agent is anticharin.
26. The synthetic therapeutic bacteriophage according to claim 1, wherein the therapeutic agent is a peptide.
27. The synthetic therapeutic bacteriophage according to claim 26, wherein the peptide is a tumor-associated antigen (TAA).
28. The synthetic therapeutic bacteriophage according to claim 1, wherein the therapeutic agent is an enzyme that produces antitumor activity.
29. The synthetic therapeutic bacteriophage according to claim 1, wherein the therapeutic agent is cytosine deaminase.
30. A living biotherapeutic agent for producing at least one therapeutic agent, comprising a recombinant bacterial organism having a bacteriophage secretion system capable of secreting a synthetic therapeutic bacteriophage according to any one of claims 1 to 29.
31. A living biotherapeutic agent for producing a therapeutic agent, comprising a recombinant bacterial organism including a bacteriophage secretion system capable of secreting a synthetic therapeutic bacteriophage, wherein the synthetic therapeutic bacteriophage presents the therapeutic agent.
32. The living biotherapeutic agent according to claim 31, wherein the therapeutic agent is fused with a bacteriophage-coated protein.
33. The live biotherapy drug according to claim 31 or 32, wherein the recombinant bacterial organism is selected from the Enterobacteriaceae, Pseudomonadaceae, and Vibrioceae families.
34. The live biotherapy drug according to claim 31 or 32, wherein the recombinant bacterial organism is Escherichia coli.
35. The live biotherapy drug according to claim 31 or 32, wherein the recombinant bacterial organism is a tumor-targeting bacterium.
36. The live biotherapy according to claim 35, wherein the tumor-targeting bacteria are selected from E. coli Nissle 1917 strain, E. coli MG1655 strain, E. coli 83972 strain, and E. coli HU2117 strain.
37. A living biotherapy drug according to any one of claims 31 to 36, wherein a recombinant bacterial organism is biologically contained.
38. A living biotherapy drug according to claim 37, wherein a recombinant bacterial organism is the nutrient requirement.
39. A living biotherapy according to any one of claims 31 to 38, wherein the recombinant bacterial organism is deficient in one or more proteases.
40. A live biotherapy drug according to any one of claims 31 to 39, wherein the recombinant bacterial organism is attenuated.
41. A living biotherapeutic agent according to any one of claims 31 to 40, wherein the synthetic therapeutic bacteriophage is a filamentous bacteriophage.
42. A living biotherapeutic agent according to any one of claims 31 to 41, wherein the bacteriophage secretion system includes a bacteriophage mechanism.
43. The living biotherapeutic agent according to claim 42, wherein the bacteriophage mechanism comprises a bacteriophage assembly module, a bacteriophage replication module, a bacteriophage coating module, and a therapeutic module.
44. A living biotherapeutic agent according to claim 43, wherein the therapeutic module comprises a therapeutic agent which will be presented by a synthetic therapeutic bacteriophage.
45. The living biotherapy according to claim 44, wherein the therapeutic module comprises one or more bacteriophage coating genes selected from gpIII, gpVI, gpVII, gpVIII, and gpIX or parts thereof, each encoding or a portion thereof of the coating proteins pIII, pVI, pVII, pVIII, and pIX.
46. A living biotherapeutic agent according to any one of claims 43 to 45, wherein the bacteriophage mechanism further comprises a regulatory module.
47. The living biotherapeutic agent according to claim 46, wherein the regulatory module includes a regulatory element that controls the activity of a bacteriophage mechanism.
48. A method for delivering at least one therapeutic agent to a tumor site in a subject, comprising administering to a subject in need an effective amount of a synthetic therapeutic bacteriophage according to any one of claims 1 to 29 or an effective amount of a live biotherapeutic agent according to any one of claims 30 to 47.
49. A method for the prevention and / or treatment of cancer in a subject requiring the use thereof, comprising administering to the subject requiring the use thereof an effective amount of a synthetic therapeutic bacteriophage according to any one of claims 1 to 29 or an effective amount of a live biotherapeutic agent according to any one of claims 30 to 47.
50. Cancers include adrenal cancer, adrenocortical carcinoma, anal cancer, appendiceal cancer, bile duct cancer, bladder cancer, bone malignancies, brain malignancies, bronchial tumors, central nervous system tumors, breast cancer, Castleman disease, cervical cancer, colon cancer, rectal cancer, colorectal cancer, endometrial cancer, esophageal cancer, eye malignancies, gallbladder cancer, gastrointestinal cancer, gastrointestinal carcinoid tumors, gastrointestinal stromal tumors, gestational trophoblastic disease, cardiac malignancies, Kaposi's sarcoma, kidney cancer, pharyngeal cancer, hypopharyngeal cancer, leukemia, liver cancer, lung cancer, lymphoma, malignant mesothelioma, multiple myeloma, and myelodysplasia. The method according to claim 49, selected from syndromes, nasal cavity cancer, paranasal sinus cancer, nasopharyngeal cancer, neuroblastoma, oral cancer, oropharyngeal cancer, osteosarcoma, ovarian cancer, pancreatic cancer, penile cancer, pituitary tumor, prostate cancer, retinoblastoma, rhabdomyosarcoma, rhabdoid tumor, salivary gland cancer, sarcoma, skin cancer, small intestine cancer, gastric cancer, teratoma, testicular cancer, pharyngeal cancer, thymic cancer, thyroid cancer, rare childhood cancers, urethral cancer, uterine cancer, uterine sarcoma, vaginal cancer, vulvar cancer, Waldenström macroglobulinemia, and Wilms tumor.
51. Use of an effective amount of a synthetic therapeutic bacteriophage according to any one of claims 1 to 29 or an effective amount of a live biotherapeutic agent according to any one of claims 30 to 47 for the prevention and / or treatment of cancer in a subject that requires it.
52. The use of an effective amount of a synthetic therapeutic bacteriophage or a live biopharmaceutical for the prevention and / or treatment of cancer in a subject requiring such use, wherein the synthetic therapeutic bacteriophage does not present a therapeutic agent.
53. Cancers include adrenal cancer, adrenocortical carcinoma, anal cancer, appendiceal cancer, bile duct cancer, bladder cancer, bone malignancies, brain malignancies, bronchial tumors, central nervous system tumors, breast cancer, Castleman disease, cervical cancer, colon cancer, rectal cancer, colorectal cancer, endometrial cancer, esophageal cancer, eye malignancies, gallbladder cancer, gastrointestinal cancer, gastrointestinal carcinoid tumors, gastrointestinal stromal tumors, gestational trophoblastic disease, cardiac malignancies, Kaposi's sarcoma, kidney cancer, pharyngeal cancer, hypopharyngeal cancer, leukemia, liver cancer, lung cancer, lymphoma, malignant mesothelioma, multiple myeloma, and myelodysplastic syndrome. Use according to claim 51 or 52, selected from group, nasal cavity cancer, paranasal sinus cancer, nasopharyngeal cancer, neuroblastoma, oral cancer, oropharyngeal cancer, osteosarcoma, ovarian cancer, pancreatic cancer, penile cancer, pituitary tumor, prostate cancer, retinoblastoma, rhabdomyosarcoma, rhabdoid tumor, salivary gland cancer, sarcoma, skin cancer, small intestine cancer, gastric cancer, teratoma, testicular cancer, pharyngeal cancer, thymic cancer, thyroid cancer, rare childhood cancers, urethral cancer, uterine cancer, uterine sarcoma, vaginal cancer, vulvar cancer, Waldenström macroglobulinemia, and Wilms' tumor.
54. A kit comprising a synthetic therapeutic bacteriophage according to any one of claims 1 to 29 or a live biotherapeutic agent according to any one of claims 30 to 47, together with instructions for administering the synthetic therapeutic bacteriophage or the live biotherapeutic agent.