CN-121987671-A - Application of shigella flexneri, related serotypes and preparation in preparation of anti-tumor immune activation and treatment drugs

Abstract

The invention relates to shigella flexneri, and an application of related serotypes and preparations thereof in preparing anti-tumor immune activation and treatment medicines. The shigella flexneri and the preparation thereof can inhibit tumor growth by activating the anti-tumor immune response of organisms and improving the tumor immune microenvironment, are suitable for preventing and/or treating various tumors, can be independently used and can be combined with the existing tumor therapies such as chemotherapy, radiotherapy, immunotherapy and the like to synergistically enhance the anti-tumor curative effect, and provide new microbial resources and strategies for tumor immunotherapy, thereby having important clinical application prospects.

Inventors

• FENG HAORAN
• ZHAO REN
• LIU KUN
• WANG CHANGGANG
• JIA WENQING
• XU ZHUOQING
• ZHENG FANG
• LI ZHILIANG
• Weng Ruoyu
• ZHANG TAO

Assignees

• 上海交通大学医学院附属瑞金医院

Dates

Publication Date

20260508

Application Date

20260130

Claims (10)

1. 1. Application of Shigella flexneri in preparing anti-tumor immunity activating and treating medicine is provided.
2. 2. The use according to claim 1, wherein the shigella flexneri comprises a strain with deposit number Bio-52755 or CMCC (B) 51572.
3. 3. The use according to claim 1, wherein the serotype of shigella flexneri comprises one or more of 1b, 1c, 2a, 2b, 3a, 3b, 4a, 4b, 5a, 5 b.
4. 4. The use according to claim 1, wherein the tumor comprises one or more of colorectal cancer, liver cancer, lung cancer, breast cancer, ovarian cancer, pancreatic cancer, gastric cancer, small intestine cancer, cervical cancer.
5. 5. A formulation comprising shigella flexneri as claimed in any one of claims 1 to 4, characterized in that the formulation comprises one or more of inactivated bacteria, metabolites, fermentation broth, supernatant.
6. 6. A pharmaceutical composition comprising shigella flexneri of any one of claims 1-4.
7. 7. The pharmaceutical composition of claim 6, wherein, the pharmaceutical composition also comprises pharmaceutically acceptable auxiliary materials.
8. 8. The pharmaceutical composition according to claim 7, wherein the auxiliary material is selected from one or more of diluents, dispersants, excipients, stabilizers, lubricants, disintegrants.
9. 9. The pharmaceutical composition of claim 6, further comprising an additional therapeutic agent selected from one or more of a chemotherapeutic agent, an immune checkpoint inhibitor, an immune cell therapy agent, an iron death inducer, a KRAS inhibitor, a radiation sensitizer.
10. 10. The pharmaceutical composition of claim 6, wherein the dosage form of the pharmaceutical composition comprises a parenteral dosage form and/or a parenteral dosage form.

Description

Application of shigella flexneri, related serotypes and preparation in preparation of anti-tumor immune activation and treatment drugs Technical Field The invention belongs to the technical field of tumors, and in particular relates to application of shigella flexneri, related serotypes and preparations thereof in preparation of anti-tumor immune activation and treatment medicines. Background Colorectal cancer (Colorectal Cancer, CRC) is one of the most common digestive tract malignancies worldwide, with the third most common incidence, and mortality next to lung cancer. In recent years, immune checkpoint inhibitors, such as anti-PD-1 therapies, have demonstrated significant efficacy in a variety of tumors, but the therapies are currently only effective in CRC patients with high microsatellite instability (MSI-H). About 85% of CRC patients clinically manifest microsatellite stabilization (MSS) type, and have poor response and prognosis to existing immunotherapy. Therefore, finding a new strategy that can overcome the drug resistance of MSS-type CRC immunotherapy has become a critical issue to be addressed in this field. Tertiary lymphoid structures (Tertiary Lymphoid Structures, TLS) are ectopic lymphoid aggregates formed in chronically inflamed tissues such as tumors. Studies have shown that the presence of TLS in a variety of malignancies is closely related to the prolongation of patient survival, enhanced immune cell infiltration, and enhanced immune checkpoint inhibitor therapeutic response. In colorectal cancer, TLS formation is considered an important marker of anti-tumor immune activation and predicts a good prognosis. However, the mechanism of TLS formation in the tumor microenvironment is not yet defined, and in particular the key regulatory factors driving its maturation remain unexplained, which limits the development of TLS-induced immunotherapeutic strategies. In recent years, the role of intestinal and tumor tissue resident microbiota in regulating tumor immunity and therapeutic response has been of increasing interest. Studies have suggested that specific microorganisms can influence tumor progression by modulating immune cell function, but whether and how they are involved in induction and maturation of TLS, especially for immunotherapeutic resistant MSS-type CRC, have not been clearly reported. At present, no key microbial strains have been found that specifically induce TLS formation and are useful for enhancing the immunotherapeutic effect. Disclosure of Invention The invention aims to solve the technical problem of providing the shigella flexneri, the related serotypes and the application of the preparation in preparing anti-tumor immune activation and treatment medicaments, wherein the strain and the preparation can effectively inhibit tumor growth by remodelling tumor immune microenvironment, particularly inducing the formation of functional TLS, and can be used together with the existing therapies (such as chemotherapy, radiotherapy and immunotherapy) to play a synergistic effect. In a first aspect, the invention provides the use of shigella flexneri in the preparation of an anti-tumour immune activation and treatment medicament. Preferably, the shigella flexneri comprises a strain deposited under accession number Bio-52755 or CMCC (B) 51572. Preferably, the serotype of shigella flexneri comprises one or more of 1b, 1c, 2a, 2b, 3a, 3b, 4a, 4b, 5a, 5 b. More preferably, the shigella flexneri serotype 1b. Further, the strain or its associated serotype is capable of activating anti-tumor immunity and/or inducing tertiary lymphoid structure formation. Preferably, the tumor comprises one or more of colorectal cancer, liver cancer, lung cancer, breast cancer, ovarian cancer, pancreatic cancer, gastric cancer, small intestine cancer and cervical cancer. More preferably, the tumor comprises various digestive tract tumors including intestinal cancer, gastric cancer and small intestinal cancer. Further, the colorectal cancer is a microsatellite stabilized colorectal cancer. In a second aspect, the invention provides a preparation comprising the shigella flexneri, wherein the preparation comprises one or more of inactivated bacteria, metabolites, fermentation culture solution and supernatant. Preferably, the amount of cells contained in a unit dose of the formulation is 1X 10≡6CFU to 1X 10≡11CFU. In a third aspect, the invention provides a pharmaceutical composition comprising the shigella flexneri. Preferably, the pharmaceutical composition further comprises pharmaceutically acceptable excipients. Preferably, the auxiliary materials are selected from one or more of diluents, dispersants, excipients, stabilizers, lubricants and disintegrants. Preferably, the pharmaceutical composition further comprises other therapeutic agents selected from one or more of chemotherapeutic agents, immune checkpoint inhibitors, immune cell therapeutic agents, iron death inducers, KRAS inhibitors, radiotherapy sens