US 2019/0054110 A1 · MODULATORS OF CCR9 FOR TREATING TUMOR RESISTANCE TO IMMUNE RESPONSES

Abstract

The present invention pertains to novel modulators of tumor resistance against T-cell mediated cytotoxic immune responses. The invention provides antagonists of tumor immune escape mechanisms and methods and other aspects related thereto, and therefore provides novel approaches for treating or aiding a treatment of various cancerous diseases and/or the diagnosis thereof. The invention specifically discloses C—C chemokine receptor type 9 (CCR9) as a checkpoint molecule in tumor resistance against cytotoxic T-cells. Provided is the inhibition of CCR9 expression, CCR9 signalling and/or CCR9-T-Cell interaction and inhibitors or antagonists thereof. In particular aspects, the invention provides combination therapeutics and/or therapies involving such inhibitors or antagonists. The invention furthermore provides screening methods for novel cancer therapeutics modulating CCR9 action, diagnostic approaches to detect cancer resistance to cytotoxic T-cells as well as pharmaceutical compositions and diagnostic kits for performing, for use with or related to these methods.

Claims41

Dependent claims

A combination comprising (a) and (b);

or (a) and (c);
or (a), (b) and (c);
wherein
(a) Is an inhibitor or antagonist of CCR9,
(b) Is an inhibitor or antagonist of PI3K-Akt signaling and/or an inhibitor or antagonist of p70S6 kinase signaling, and
(c) Is an activator or agonist of ERK1/2 signaling and/or an activator or agonist of JNK signaling.

3 more elements

A method for identifying a compound suitable for the treatment of a tumor disease, the method comprising the steps of

(a) Providing a first cell expressing a CCR9 protein on the cellular surface,
(b) Providing a candidate compound,
(c) Optionally, providing a second cell which is a cytotoxic T-lymphocyte (CTL), preferably that is capable of immunologically recognizing said first cell, and
(d) Bringing into contact the first cell and the candidate compound, and optionally the second cell, and
(e) Determining subsequent to step (d), either or both of:
i. CCR9 expression in said first cell, wherein a reduced CCR9 expression in said first cell contacted with the candidate compound compared to said first cell not contacted with said candidate compound indicates that the candidate compound is a compound suitable for the treatment of a tumor disease;
and/or
ii. cytotoxicity of said CTL against said first cell, wherein an enhanced cytotoxicity of said CTL against said first cell contacted with the candidate compound compared to the cytotoxicity of said CTL against said first cell not contacted with the candidate compound indicates that the candidate compound is a compound suitable for the treatment of a tumor disease.

5 more elements

A method for treating a tumor disease in a patient, wherein said tumor disease is characterized by resistance of said tumor against immune responses, the method comprising a step of inhibiting in said patient CCR9 expression in said tumor, and/or inhibiting in said patient CCR9 mediated interaction of at least one tumor cell of said tumor with at least one T-cell of said patient, and/or inhibiting in said patient CCR9 signaling in said tumor.

A method for aiding a patient's immune response against a tumor disease comprising a step of inhibiting in said patient CCR9 expression in said tumor, and/or inhibiting in said patient CCR9 mediated interaction of at least one tumor cell of said tumor with at least one T-cell of said patient, and/or inhibiting in said patient CCR9 signaling in said tumor.

Dependencies are inferred from the claim text.

Modulators of ccr9 for treating tumor resistance to immune responses

Life of this patent

Modulators of ccr9 for treating tumor resistance to immune responses

Life of this patent

Abstract

Claims41