Lactobacillus paracasei strain for enhancing treatment effect of immune checkpoint inhibitor and application of lactobacillus paracasei strain

A technology for enhancing immunity and paracheese, applied in Lactobacillus, bacteria used in food preparation, applications, etc., can solve the problem of unclear mechanism of ICI therapeutic effect, improve intestinal microecology, increase infiltration and activation, The effect of promoting the therapeutic effect

Pending Publication Date: 2022-05-27
SHANGHAI YAODAN BIOTECHNOLOGY CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Although preclinical animal experiments and clinical small-sample studies have found that gut microbiota affects the therapeutic effect of ICI, the mechanism by which gut microbiota affects the therapeutic effect of ICI is still unclear.

Method used

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  • Lactobacillus paracasei strain for enhancing treatment effect of immune checkpoint inhibitor and application of lactobacillus paracasei strain
  • Lactobacillus paracasei strain for enhancing treatment effect of immune checkpoint inhibitor and application of lactobacillus paracasei strain
  • Lactobacillus paracasei strain for enhancing treatment effect of immune checkpoint inhibitor and application of lactobacillus paracasei strain

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Example 1. Gut flora from healthy donors enhances the antitumor effect of PD-1 antibody

[0028]In C57BL / 6 mice, an antibiotic combination (ATB) consisting of vancomycin, neomycin, metronidazole, and ampicillin was first treated for 7 days to clear the mouse gut microbiota; then the guts of healthy donors were administered 20 μl of microflora was administered by gavage for 10 days, and 20 μl of intestinal microflora of tumor patients was used as a control; then, mice were inoculated with MC38 cells, and tumor volume was measured twice a week after tumor inoculation, and tumor growth curves were drawn; after 7 days, tumors were Size 150-200mm 3 , treated with PD-1 antibody for 21 days; 28 days after tumor seeding, tumor size was assessed, mice were sacrificed, and intestinal, blood, spleen, colon and stool samples were taken from mice.

[0029] figure 1 For PD-1 antibody to have better anti-tumor effect in tumor-bearing mice transplanted with healthy donor gut flora, (...

Embodiment 2

[0031] Example 2. Correlation between intestinal flora and the therapeutic effect of PD-1 antibody

[0032] Lactobacillus in healthy donors was significantly higher than that in tumor patients, and was positively correlated with the therapeutic effect of anti-PD-1 antibodies.

[0033] The gut, blood, spleen, colon, and fecal samples of mice with gut microbiota constructed from the gut microbiota of the above tumor patients and healthy donors were collected. 16S was used to sequence the intestinal flora in stool samples, and analyze the expression of cytokines and the number and classification of immune cells in mice treated with PD-1 antibody, to explore the relationship between the intestinal flora and the therapeutic effect of PD-1 antibody. Correlation. We found a taxonomic tree of gut microbiota ( image 3 A), LDA score ( image 3 B), genus level analysis ( image 3 C), relative abundance comparison ( image 3 D) All indicated that lactic acid bacteria in the intestin...

Embodiment 3

[0034] Example 3. A new strain of L. paracasei L. paracasei-sh2020 from healthy donors enhances the anti-tumor effect of PD-1 antibody

[0035] Using MRS lactic acid bacteria selective medium, we isolated and cultured fecal samples from healthy donors with good PD-1 antibody promoting effect, and we obtained multiple strains of lactic acid bacteria that can be efficiently amplified. Next, we treated C57BL / 6 mice with an antibiotic combination (ATB) consisting of vancomycin, neomycin, metronidazole and ampicillin for 7 days to clear the intestinal flora of the mice; 20 μl of .paracasei-sh2020 was administered by gavage for 10 days, and 20 μl of other lactic acid bacteria species and the intestinal flora of healthy donors were administered as controls; then, mice were inoculated with MC38 cells, and tumor volumes were measured twice a week after tumor inoculation, and plotted Tumor growth curve; tumor size 150-200mm after 7 days 3 , treated with PD-1 antibody for 21 days; 28 da...

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Abstract

The invention provides a lactobacillus paracasei strain capable of enhancing the treatment effect of an immune checkpoint inhibitor and application of the lactobacillus paracasei strain. The lactobacillus paracasei strain is named as lactobacillus paracasei 2020 (hereinafter referred to as L.paracasei-sh2020), and the preservation number of the lactobacillus paracasei strain is CCTCC (China Center for Type Culture Collection) NO: M 2020474. The lactobacillus paracasei-sh2020 provided by the invention can be used for improving the intestinal microecology of a tumor model mouse, promoting tumor cells to express CXCL10 chemotactic factors, collecting and increasing the infiltration and activation of killer CD8T lymphocytes in tumor cell tissues, efficiently promoting the treatment effect of a PD-1 antibody and remarkably inhibiting the growth of tumors.

Description

technical field [0001] The invention belongs to the field of biotechnology, and in particular relates to a Lactobacillus paracasei strain for increasing the therapeutic effect of an immune checkpoint inhibitor and its application. Background technique [0002] Immune checkpoint inhibitors (ICIs) are monoclonal antibodies targeting corresponding immune checkpoints, blocking the inhibitory effect of tumor cells on immune cells through immune checkpoints, enabling immune cells to kill tumor cells effect. There are currently 3 types of ICIs approved for marketing, including programmed death-1 (PD-1) monoclonal antibody, programmed death ligand-1 (PD-L1) monoclonal antibody, and cell Toxic T-lymphocyte associated protein-4 (cytotoxic T-lymphocyte associated protein 4, CTLA-4) monoclonal antibody. ICI has been used to treat a variety of tumors since its inception, and has achieved positive effects in 20%-30% of patients. Some patients with advanced tumors even have complete remi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N1/20A23L33/135A61K35/747A61P35/00C12R1/245
CPCC12N1/20A23L33/135A61K35/747A61P35/00A23V2002/00A23V2400/125A23V2200/308Y02A50/30
Inventor 王立顺韩冰张世龙
Owner SHANGHAI YAODAN BIOTECHNOLOGY CO LTD
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