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Compositions and methods for enhancing immunotherapy and vaccine efficacy

A therapy and vaccine technology, applied in the direction of non-active ingredients of polymer compounds, drug combinations, medical raw materials derived from bacteria, etc.

Pending Publication Date: 2022-07-08
RGT UNIV OF MICHIGAN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, immune checkpoint therapy works for only a fraction of patients (typically 10-30%)

Method used

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  • Compositions and methods for enhancing immunotherapy and vaccine efficacy
  • Compositions and methods for enhancing immunotherapy and vaccine efficacy
  • Compositions and methods for enhancing immunotherapy and vaccine efficacy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment I

[0163] This example demonstrates the improved efficacy of immune checkpoint blockers and prebiotics in a preventative setting.

[0164] From the FDA's list, five candidate materials were selected for initial screening. Melatonin, present in the pineal gland and gastrointestinal tract, regulates sleep cycles and circadian rhythms. Epigallocatechin gallate (EGCG) is a natural antioxidant found in plants. Fucoidan, oligofructose and inulin are plant polysaccharides widely used in food and dietary supplements. These candidate materials were first tested for their ability to improve the antitumor efficacy of alpha-PD-1 therapy in a preventive manner. WT Balb / c mice were treated with these materials via oral gavage one week before tumor inoculation ( figure 1 A). All these agents showed stronger antitumor efficacy in combination with α-PD-1 therapy than with α-PD-1 alone, and inulin showed the best efficacy ( figure 1 B and C). Combination of inulin with α-PD-1 prolonged anima...

Embodiment II

[0167] This example describes the improved efficacy of immune checkpoint blockers and prebiotics in a therapeutic setting.

[0168] Having identified inulin as a promising candidate, these agents were next tested in a therapeutic setting. After inoculation of Balb / c mice with CT-26 cells, tumor-bearing mice were treated by oral gavage from day 7 ( figure 2 A). Consistent with prophylactic treatment, inulin combined with α-PD-1IgG showed the strongest antitumor efficacy ( figure 2 B and C), and prolonged animal survival ( figure 2 D). Inulin also elicited significantly higher AH1-specific CD8 in PBMCs at days 18 and 24 + T cells ( figure 2 E-G).

Embodiment III

[0170] This example describes the dose effect of inulin and melatonin.

[0171] The dose effects of inulin and melatonin, which are the top 2 candidates identified above, were next examined. Halving the doses of inulin and melatonin (ie, inulin 60 mg and melatonin 50 mg / Kg) did not impair their efficacy against tumor growth in combination with α-PD-1 ( image 3 A, B), indicating a relatively wide therapeutic window for inulin and melatonin. Similar results were found in the frequency of AH1-specific CD8+ T cells in PBMCs ( image 3 C, D). Since tumor-infiltrating lymphocytes play a key role in the outcome of immunotherapy, T lymphocytes in the tumor microenvironment were examined. Inulin or melatonin treatment in combination with α-PD-1IgG significantly enhanced intratumoral infiltration of T cells compared with α-PD-1IgG alone ( image 3 E-H).

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Abstract

The present invention relates generally to compositions and methods for enhancing the efficacy of immunotherapy and vaccines. In particular, the present invention relates to increasing the richness and diversity of the gut microbiome of a subject by administering an agent (e.g., a prebiotic agent comprising fibers (e.g., epigallocatechin gallate (EGCG), fucoidin, potato starch, fructo-oligosaccharide and synanthrin)) (e.g., melatonin) with an immunotherapy or vaccine. Such compositions and methods are useful for the treatment of cancer, infectious pathogens, autoimmune diseases, neurological disorders, and / or obesity.

Description

technical field [0001] The present invention generally relates to compositions and methods for enhancing the efficacy of immunotherapy and vaccines. In particular, the present invention relates to administration of pharmaceutical agents (eg, prebiotic agents comprising fiber (eg, epigallocatechin gallate (EGCG), fucoidan, potato starch, fructooligosaccharides, and inulin)) (eg, , melatonin) and immunotherapy or vaccines to enhance the richness and diversity of the gut microbiome in subjects. Such compositions and methods can be used to treat cancer, infectious pathogens, autoimmune diseases, neurological disorders and / or obesity. Background technique [0002] Cancer immunotherapy is revolutionizing the field of oncology. However, immune checkpoint therapy works only in a subset of patients (usually 10-30%). There is a great need to improve the efficacy of immune checkpoint blockade. In addition, there is broad research interest in improving vaccines. [0003] The presen...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61K31/733A61K31/732A61K35/74A61K31/737A61K31/738A61K31/4045A61K47/42A61K9/06A61K47/36A61K47/10A61K31/353A61P35/00A61P35/02
CPCA61K35/74A61K39/39A61P35/00A61K9/06A61K47/10A61K47/36A61K47/42A61K31/353A61K31/737A61K31/733A61K31/4045A61K31/732A61K31/738A61K2300/00A61K31/718A61K39/395A61K39/0011A61K45/06A61K9/0053A61K35/745A61K35/747A61K2035/115A61K2039/505A61K2039/55511A61K2039/55583C07K16/2818
Inventor 詹姆斯·J·穆恩韩凯徐进黄学辉
Owner RGT UNIV OF MICHIGAN
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