Mucispirillum compositions and cancer treatment methods thereof
AssigneePresident and Fellows of Harvard College
InventorsWendy Sarah GARRETT, Lior LOBEL
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Abstract
The technology described herein is directed to compositions comprising Mucispirillum (e.g., M. schaedleri). Also described herein are methods of treating cancer using Mucispirillum compositions; a diet high in sulfur amino acids (SAA) or a supplement comprising SAAs; and/or XCL1 polypeptides (or XCR1 agonists). Also described herein are cancer treatment stratification methods related to detection of the level of M. schaedleri, XCL1 polypeptide, NKTs, and/or CD103+ cDC1s, and alteration or stratification of treatment accordingly.
Claims80
A composition comprising Mucispirillum schaedleri (M. schaedleri) bacteria formulated for delivery to the intestine.
A composition comprising live M. schaedleri bacteria, dead M. schaedleri bacteria, conditioned M. schaedleri culture medium, or an organic solvent extract of conditioned M. schaedleri culture medium or a fraction thereof that promotes XCL1 secretion by NKT cells, wherein the composition is formulated for delivery to the intestine.
A method of increasing CD8+ T cell infiltration in a colorectal tumor, the method comprising administering a diet high in sulfur amino acids (SAA) or a supplement comprising SAAs to a subject in need thereof.
A method of establishing or maintaining a tumor-suppressive gut environment in a subject in need thereof, the method comprising administering a diet high in sulfur amino acids (SAA) or a supplement comprising SAAs.
A method of treating cancer, the method comprising administering to a subject in need thereof an XCL1 polypeptide.
A method of treating cancer, the method comprising administering to a subject in need thereof a microorganism engineered to express XCL1 polypeptide.
A method of treating cancer, the method comprising administering to a subject in need thereof an agonist of the XCL1 receptor, XCR1.
A method of stratifying a subject for cancer treatment, the method comprising:
- detecting the level of M. schaedleri in a sample from the subject;
- and
- classifying the subject as high risk if the level of M. schaedleri is below a pre-determined threshold;
- or
- classifying the subject as low risk if the level of M. schaedleri is at or above a pre-determined threshold.
A method of stratifying a subject for cancer treatment, the method comprising:
- obtaining results from an assay detecting the level of M. schaedleri in a sample from the subject;
- and
- classifying the subject as high risk if the level of M. schaedleri is below a pre-determined threshold;
- or
- classifying the subject as low risk if the level of M. schaedleri is at or above a pre-determined threshold.
A method of stratifying a subject for cancer treatment, the method comprising:
- detecting the level of XCL1 polypeptide, NKTs, and/or CD103+ cDC1s in a sample from the subject;
- and
- classifying the subject as high risk if the level of XCL1 polypeptide, NKTs, and/or CD103+ cDC1s is below a pre-determined threshold;
- or
- classifying the subject as low risk if the level of XCL1 polypeptide, NKTs, and/or CD103+ cDC1s is at or above a pre-determined threshold.
A method of stratifying a subject for cancer treatment, the method comprising:
- obtaining results from an assay detecting the level of XCL1 polypeptide, NKTs, and/or CD103+ cDC1s in a sample from the subject;
- and
- classifying the subject as high risk if the level of XCL1 polypeptide, NKTs, and/or CD103+ cDC1s is below a pre-determined threshold;
- or
- classifying the subject as low risk if the level of XCL1 polypeptide, NKTs, and/or CD103+ cDC1s is at or above a pre-determined threshold.
An enteric delivery formulation comprising at least one metabolite selected from FIG. 4H, FIG. 4I, or FIG. 16.
An enteric delivery formulation comprising at least one metabolite selected from the group consisting of:
- succinic acid;
- propionic acid;
- nicotinic acid;
- aconitic acid (cis and/or trans);
- pentadecanoic acid;
- itaconic acid;
- 16-hydroxyhexadecanoic acid;
- C8H15NO3S;
- crotonic acid;
- myristic acid;
- 17-hydroxyheptadecanoic acid (C17H34O3);
- and 15-hydroxpentadecanoic acid (C15H30O3).
An enteric delivery formulation comprising at least one metabolite selected from the group consisting of:
- succinic acid;
- nicotinic acid;
- aconitic acid (cis and/or trans);
- pentadecanoic acid;
- itaconic acid;
- 16-hydroxyhexadecanoic acid;
- and crotonic acid.
Dependencies are inferred from the claim text.