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Compositions and methods for inducing CD8 + T cells

A technology of a composition and mixture, applied in the field of compositions and methods for inducing CD8+ T cells, can solve the problems of unresponsiveness to cancer immunotherapy and the like

Pending Publication Date: 2020-11-03
KEIO UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, a large percentage of patients do not respond to cancer immunotherapy

Method used

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  • Compositions and methods for inducing CD8 + T cells
  • Compositions and methods for inducing CD8 + T cells
  • Compositions and methods for inducing CD8 + T cells

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0498] Example 1: Identification of a bacterial mixture that induces CD8+ T cells

[0499] figure 1 showed that CD8 T cells expressing IFN-γ were found in various organs. This population typically constitutes 15% of CD8 T cells in lymphoid and nonlymphoid organs and more than 50% in the intestinal lamina propria. This frequency was found to be significantly lower in the colon and small intestine of germ-free mice ( figure 2 ), suggesting that the microbiota plays a role in the accumulation of IFN-+CD8+ T cells in the intestine.

[0500] image 3showed that IFN+CD8+ between SPF C57BL / 6 mice purchased from Charles River Laboratories Inc. The frequency of T cells varies. When SPF C57BL / 6 mice from Charles River Laboratories were housed with CLEA mice in the same cage, an increase in IFN+CD8+ T cells was observed in mice delivered from Charles River Laboratories ( image 3 ). This finding strongly supports the hypothesis that specific microbial species exist in the mouse m...

Embodiment 1A

[0504] Example 1A: Further characterization of a mixture of 11 strains

[0505] The strains in Table 1 were further characterized by resequencing the 16S sequence and by whole genome sequencing. Table 2 lists the results of further characterization.

[0506] Table 2 Further characterization of 11-blend (mixture of 11 strains)

[0507]

Embodiment 2

[0508] Example 2: Further Characterization of Bacterial Mixtures Inducing CD8+ T Cells

[0509] Figure 15 Twenty-six strains isolated from cecal contents of B#5+AMP mice showing high frequency of IFNγ+CD8+ T cells are shown. Of these 26 strains, 11 strains ("11 mix") were positively correlated with the frequency of IFNγ+CD8+ T cells. Therefore, these 11 strains were selected for further experiments, and a mixture of the 11 strains ("11-mix") was inoculated into germ-free mice (see also Table 2). Colonization with the 11-mix resulted in a strong induction of colonic IFNγ+CD8+ T cells, whereas the other 10 strains (“10-mix”) weakly induced IFNγ+CD8+ T cells and GzmB compared to the induction level of the 11-mix +CD8+T cells ( Figure 22-24 ).

[0510] A phylogenetic comparison using 16S rRNA gene sequences revealed that the 11-strain mixture (also referred to as "11-mixture") consisted of 7 strains belonging to the order Bacteroidetes ("7 strains") and 4 strains belonging t...

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Abstract

Provided herein are compositions and methods for the induction and / or proliferation of CD8+ T-cells. The disclosure also provides methods of treatment of diseases that can be treated by the inductionand / or proliferation of CD8+ T-cells.

Description

technical field [0001] Pursuant to 35 U.S.C. §119(e), this application claims U.S. Provisional Application No. 62 / 628,501 filed February 9, 2018, U.S. Provisional Application No. 62 / 673,436 filed May 18, 2018, and Sept. 27, 2018 U.S. Provisional Application No. 62 / 737,318 filed on November 5, 2018, and U.S. Provisional Application No. 62 / 795,506 filed on January 22, 2019. The entire content of each of these referenced applications is incorporated herein by reference. [0002] The present disclosure relates to compositions and methods for inducing and / or expanding CD8+ T cells. The present disclosure also provides methods of treating diseases that can be treated by inducing and / or expanding CD8+ T cells. Background technique [0003] Animals, including humans, contain many microorganisms (collectively called the microbiota) in anatomical locations including the mouth, esophagus, stomach, small intestine, large intestine, cecum, vagina, skin, nasal cavity, ear, and lungs. T...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N1/20A61K35/74A61K39/395A61K39/39A61K45/06A61P31/00A61P35/00A23L33/135
CPCA61P31/00A61P35/00C12N1/20A23L33/135A61K39/39A61K2039/55594C07K16/2818A61K2039/505C07K2317/76A61K39/39558A61K45/06A61K35/74A61K2300/00A61P31/04A61K35/741A61K39/3955A61K2035/115
Inventor 本田贤也田之上大河上裕新幸二森田觉A·N·斯凯利
Owner KEIO UNIV