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Intestinal flora relevant to irAE and method for treating and preventing irAE

A technology of bacteria and Lactobacillus, applied in the field of immunotherapy, can solve the problems of patient death, lack of safe and effective treatment options, etc.

Pending Publication Date: 2019-07-30
SHANGHAI HUMAP MEDICAL TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The occurrence of irAE can affect or interrupt the progress of ICB or CAR-T treatment, and severe cases can lead to the death of patients treated with ICB or CAR-T
At present, in addition to giving corticosteroids or other immunosuppressive drugs to patients with severe irAEs, there is still a lack of targeted, safe and effective treatment options for related side effects.

Method used

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  • Intestinal flora relevant to irAE and method for treating and preventing irAE
  • Intestinal flora relevant to irAE and method for treating and preventing irAE
  • Intestinal flora relevant to irAE and method for treating and preventing irAE

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0079] Example 1: Effects of adding ICB drugs on mouse body weight, survival rate and key inflammatory factors on the basis of DSS model

[0080] In order to simulate the intestinal side effects caused by ICB clinically, in this example, mice were co-treated with ICB and DSS to establish an intestinal irAE model. According to the mouse survival curve ( figure 1 , A) It can be seen that the survival rate of mice added with ICB on the basis of DSS induction was significantly lower than that of DSS alone (Pfigure 1 , B). The above results indicated that ICB treatment of DSS mouse model can successfully simulate the clinical side effects caused by ICB treatment.

Embodiment 2

[0081] Example 2: Effect of ICB drugs on intestinal flora of mice

[0082] In order to observe the correlation between the intestinal side effects caused by ICB and the intestinal flora, three groups were collected in this example, namely the normal non-treatment group mice (Nor), the DSS alone group (Ctrl), and the DSS combined with ICB induction group. Fresh fecal samples from mice in the enteritis group (ICB) were used, and the intestinal flora in each group of mice were detected by 16S rDNA sequencing. The results showed that there were significant differences in the composition of intestinal bacteria in the mice of Ctrl group or ICB group compared with the mice of Nor group ( figure 2 , A and B). Among them, comparing the DSS single-use and no-treatment groups, the genera Lactobacillus, Alistipes, Olsenella, Turicibacter and Clostridium sensu stricto in the ICB treatment group decreased progressively, while the genera Escherichia / Shigella, Bacteroides, Veillonella, Flav...

Embodiment 3

[0083] Example 3: Comparison of survival period and key serum inflammatory factor levels between transgenic mice and wild-type mice

[0084] Depend on image 3 (A) It can be seen that the survival time of Foxp3 knockout mice (MT) is significantly shorter than that of wild-type mice (WT). At the same time, the levels of key inflammatory cytokines such as TNF-α, IL-2 and IFN-γ in the serum of Foxp3 knockout mice were significantly increased ( image 3 , B), suggesting that the systemic inflammatory response is obvious. This transgenic mouse-strain can mimic the clinical systemic immune side effects caused by ICB treatment.

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Abstract

The invention discloses an intestinal flora. The key intestinal bacterial genus for relevant adverse reactions influencing tumor immnuotherapy is identified. The key intestinal bacterial genus can serve as a detection index to diagnose and predict the relevant adverse reactions caused by tumor immnuotherapy and can be used for preventing, relieving or treating the relevant adverse reactions duringtumor immnuotherapy.

Description

technical field [0001] The invention belongs to the field of immunotherapy, and in particular relates to intestinal flora related to adverse reactions related to tumor immunotherapy and methods for treating and preventing adverse reactions related to tumor immunotherapy. Background technique [0002] Immunotherapy represented by Immune Checkpoint Blockade (ICB) is the latest and most effective method in the field of malignant tumor treatment. However, with the widespread application of ICB in the treatment of various tumors, and the emergence of other tumor immunotherapies such as vaccines and chimeric antigen receptor T-cells (CAR T), one of the biggest clinical problems is that the incidence rate can be as high as 80.2% of immune-related adverse reactions (Immune-Related Adverse Events, irAE), that is, side effects of immunotherapy. A recent evaluation study on the lethal side effects of immune checkpoint inhibitors published in the top medical oncology journal JAMA Oncol...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K35/745A61K35/747A61K35/74A61P35/00A61P1/00C12Q1/689C12Q1/06C12Q1/10C12R1/185C12R1/225C12R1/01C12R1/22C12R1/145C12R1/38
CPCA61K35/745A61K35/747A61K35/74A61P35/00A61P1/00C12Q1/689A61K2300/00Y02A50/30
Inventor 袁向亮何宝坤于亮
Owner SHANGHAI HUMAP MEDICAL TECH CO LTD