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Application of bacteria in preparation of synergist of immune checkpoint inhibitor

A technology of bacteria and bacterial metabolites, which is applied in the field of cancer treatment, can solve the problems of less drug responders, less drug responders in the range of tumor types, and easy metastasis and recurrence, so as to expand the number of beneficiary tumor patients, prolong the overall survival time, The effect of increasing the response rate

Active Publication Date: 2022-03-11
SUN YAT SEN UNIV CANCER CENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] The treatment method given by the present invention has obvious improvements for the shortcomings of conventional therapy: large toxic and side effects, easy transfer and recurrence, short duration, short survival period, and poor quality of life; for the shortcomings of immune checkpoint monotherapy: The range of tumor types is limited and the number of drug responders is small, which has been significantly improved; the disadvantages of combined radiotherapy and chemotherapy for immune checkpoints: large toxic and side effects and few drug response populations have been significantly improved

Method used

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  • Application of bacteria in preparation of synergist of immune checkpoint inhibitor
  • Application of bacteria in preparation of synergist of immune checkpoint inhibitor
  • Application of bacteria in preparation of synergist of immune checkpoint inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0129] Example 1 The therapeutic effect of P. fennerii combined with immune checkpoint inhibitors on tumors

[0130] 1. Experimental method

[0131] 1. Experimental materials

[0132] (1) Mouse strain: 6-week-old female C57BL / 6J mice

[0133] (2) Tumor cell lines: mouse melanoma cell line (B16-OVA, ATCC), mouse intestinal cancer cell line (MC38, ATCC)

[0134] (3) Bacterial preparation: Alistipes finegoldii (Alistipes finegoldii, DSM No.: 17242, Typestrain, whose 16S rDNA sequence is shown in SEQ ID NO: 1), referred to as Af, commercially purchased from DSMZ German National Culture Collection Center, (official website of DSMZ: http: / / www.dsmz.de).

[0135](4) Bacterial culture medium: liquid DSMZ104 medium, the formula mainly includes peptone, yeast extract, beef extract and glucose, etc., commercially purchased from DSMZ German National Culture Collection Center.

[0136] (5) Immune checkpoint inhibitor: PD-1 monoclonal antibody (αPD-1), clone number G4C2, the reagent was...

Embodiment 2

[0157] Example 2 Prolongation of overall survival time by different doses of Bacillus fennerii combined with different immune checkpoint inhibitors

[0158] 1. Experimental method

[0159] 1. Experimental materials

[0160] (1) Mouse strain: 6-week-old female C57BL / 6J mice

[0161] (2) Tumor cell lines: mouse melanoma cell line (B16-OVA, ATCC), mouse intestinal cancer cell line (MC38, ATCC)

[0162] (3) Bacterial preparation: Alistipes finegoldii (Alistipes finegoldii, DSM No.: 17242, Typestrain, whose 16S rDNA sequence is shown in SEQ ID NO: 1), referred to as Af, commercially purchased from DSMZ German National Culture Collection center.

[0163] (4) Bacterial culture medium: liquid DSMZ104 medium, the formula mainly includes peptone, yeast extract, beef extract and glucose, etc., commercially purchased from DSMZ German National Culture Collection Center.

[0164] (5) Immune checkpoint inhibitor: PD-1 monoclonal antibody (αPD-1), clone number G4C2, the reagent was presen...

Embodiment 3

[0182] Example 3 Alistipes finegoldii is an endogenous intestinal commensal bacterium of humans

[0183] 1. Experimental method

[0184] Four human gut metagenomic datasets were analyzed, containing a total of 1396 human fecal samples, involving nine different types of populations. Metagenome sequencing technology can achieve the accuracy of identification of human gut bacteria level.

[0185] 9 different types of populations include: 1) healthy adults; 2) patients with colorectal adenoma; 3) patients with colorectal cancer; 4) patients after surgery for colorectal cancer; 5) patients with atherosclerotic disease; NSCLC patients before immune checkpoint inhibitors (ICIs); 7) NSCLC patients after receiving immune checkpoint inhibitors (ICIs); 8) kidney cancer before receiving immune checkpoint inhibitors (ICIs) Patient gut microbiota metagenomic data; 9) Kidney cancer patients after receiving immune checkpoint inhibitors (ICIs).

[0186] The details of the dataset are shown ...

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Abstract

The invention discloses application of bacteria in preparation of a synergist of an immune checkpoint inhibitor. According to the present invention, the human endogenous intestinal bacterium single bacterium oral preparation is combined with the immune checkpoint inhibitor, and the anti-tumor immune protection reaction is generated through the endogenous intestinal bacterium stimulation, such that the drug effect of the immune checkpoint inhibitor on a plurality of tumor species is significantly enhanced, the safety is good, the overall survival time of cancer patients is prolonged, and the treatment effect is good. The response rate of cancer immunotherapy crowds is improved, and cancer immunotherapy benefiting tumor patient crowds are expanded.

Description

technical field [0001] The invention relates to the technical field of cancer treatment, in particular to the application of a bacterium in the preparation of synergists of immune checkpoint inhibitors. Background technique [0002] Malignant tumors are one of the biggest problems facing the world at present. Among the various lethal factors that cause death every year, malignant tumors rank first. Conventional treatment options, such as surgery, radiotherapy and chemotherapy, are difficult to completely remove tumor cells, and the recurrence rate is high, and the treatment methods such as radiotherapy and chemotherapy are not targeted, so they can kill tumor cells while also killing normal cells. The killing effect causes great harm to the patient and seriously affects the quality of life of the patient. [0003] Compared with conventional therapy, the target of tumor immunotherapy is not tumor cells and tissues, but the body's own immune system. By regulating and activati...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K35/74A61K39/395A61P35/00A61P35/04C12N1/20A23L33/135A23L2/52A23K10/18C12R1/01
CPCA61K35/74A61K39/3955A61P35/00A61P35/04A23L33/135A23L2/52A23K10/18A23V2002/00A61K2300/00A23V2200/3204A23V2200/308Y02A50/30
Inventor 徐瑞华赵霞
Owner SUN YAT SEN UNIV CANCER CENT
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