Treatment and prevention of cancer using vista antigen-binding molecules
AssigneeHummingbird Bioscience Pte. Ltd.
InventorsBhushan Dharmadhikari, Olga Zharkova, Debleena Ray, Roberto Tirado-Magallanes, Dipti Thakkar, Konrad Paszkiewicz, Jerome Boyd-Kirkup, Piers Ingram
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Abstract
VISTA antigen-binding molecules are disclosed. Also disclosed are nucleic acids and expression vectors encoding, composition comprising, and methods using, the VISTA antigen-binding molecules.
Claims16
An antigen-binding molecule that binds to VISTA for use in a method of treating or preventing a cancer in a subject, wherein the treatment or prophylaxis comprises:
- (i) increasing the number and/or proportion of antigen-specific CD8+ T cells;
- (ii) increasing CD8+ T cell activity;
- (iii) reducing the level of T cell exhaustion;
- (iv) reducing the number and/or proportion of tumour-associated macrophages (TAMs);
- (v) increasing the number and/or proportion of M1-type macrophages;
- and/or
- (vi) increasing M1-type macrophage activity.
Use of an antigen-binding molecule that binds to VISTA in the manufacture of a medicament for treating or preventing a cancer in a subject, wherein the treatment or prophylaxis comprises:
- (i) increasing the number and/or proportion of antigen-specific CD8+ T cells;
- (ii) increasing CD8+ T cell activity;
- (iii) reducing the level of T cell exhaustion;
- (iv) reducing the number and/or proportion of tumour-associated macrophages (TAMs);
- (v) increasing the number and/or proportion of M1-type macrophages;
- and/or
- (vi) increasing M1-type macrophage activity.
A method of treating or preventing a cancer in a subject, wherein the method comprises administering to a subject a therapeutically or prophylactically effective amount of an antigen-binding molecule that binds to VISTA, wherein the treatment or prophylaxis comprises:
- (i) increasing the number and/or proportion of antigen-specific CD8+ T cells;
- (ii) increasing CD8+ T cell activity;
- (iii) reducing the level of T cell exhaustion;
- (iv) reducing the number and/or proportion of tumour-associated macrophages (TAMs);
- (v) increasing the number and/or proportion of M1-type macrophages;
- and/or
- (vi) increasing M1-type macrophage activity.
A method of selecting a subject for treatment with an antigen-binding molecule that binds to VISTA, comprising:
- (a) analysing a subject's cancer in order to determine whether the cancer is characterised by:
- (i) low number and/or proportion of antigen-specific CD8+ T cells;
- (ii) low CD8+ T cell activity;
- (iii) presence and/or high levels of exhausted T cells;
- (iv) presence and/or high number and/or proportion of TAMs;
- (v) low number and/or proportion of M1-type macrophages;
- and/or
- (vi) low M1-type macrophage activity;
- and
- (b) selecting a subject for treatment with an antigen-binding molecule that binds to VISTA where the subject's cancer is determined in step (a) to have one or more of (i) to (vi).
A method of determining the response in a patient to treatment with an antigen-binding molecule that binds to VISTA, comprising:
- (a) analysing a subject's cancer at a first timepoint in order to determine the:
- (i) number and/or proportion of antigen-specific CD8+ T cells;
- (ii) CD8+ T cell activity;
- (iii) level of T cell exhaustion;
- (iv) number and/or proportion of tumour-associated macrophages (TAMs);
- (v) number and/or proportion of M1-type macrophages;
- and/or
- (vi) M1-type macrophage activity;
- (b) analysing a subject's cancer at a subsequent timepoint in order to determine one or more of (i) to (vi);
- and
- (c) determining the difference between (a) and (b), wherein a(n):
- (i) increased number and/or proportion of antigen-specific CD8+ T cells;
- (ii) increased CD8+ T cells activity;
- (iii) reduced level of T cell exhaustion;
- (iv) reduced number and/or proportion of tumour-associated macrophages (TAMs);
- (v) increased number and/or proportion of M1-type macrophages;
- and/or
- (vi) increased M1-type macrophage activity,
- in (b) relative to (a) signifies a positive response to treatment with an antigen-binding molecule that binds to VISTA.
Dependencies are inferred from the claim text.