Method for treating melanoma

Patent metadata

Field	Value
Publication number	US-10144772-B2
Application number	US-201515310158-A
Country	US
Kind code	B2
Filing date	May 12, 2015
Priority date	May 12, 2014
Publication date	Dec 4, 2018
Grant date	Dec 4, 2018

Abstract

The present invention relates to a TNFα blocking agent for use in the treatment and prevention of melanoma in a subject in whom melanoma cells express MHCI and in whom stroma cells exhibit TNF expression.

First claim

The invention claimed is:

1. A method of treating melanoma in a subject in need thereof, comprising
identifying an immunocompetent subject, wherein immunocompetency is determined by finding in a tumor sample from the subject:
CD8 + tumor infiltrating lymphocytes (TIL),
a high endothelial venule (HEV) MECA79+ differentiation or density,
melanoma cells that express Major Histocompatibility Complex Class I (MHCI), and
stroma cells in contact with the melanoma cells that express tumor necrosis factor-alpha (TNFα) ;

wherein an expression level of MHCI in melanoma cells in the tumor sample from the subject is higher than a predetermined reference value, and an expression level of TNFα in stroma cells in contact with the melanoma cells in the tumor sample from the subject is higher than a predetermined reference value, and
administering to the subject a therapeutically effective amount of TNFα blocking agent.

2. A method for treating melanoma comprising the steps of
i) determining that CD8 + tumor infiltrating lymphocytes (TIL) and a high endothelial venule (HEV) MECA79+ differentiation or density are present in a melanoma tumor sample obtained from a subject, wherein an expression level of Major Histocompatibility Complex Class I (MHCI) in melanoma cells in the sample obtained from the subject is higher than a predetermined reference value and determining that an expression level of tumor necrosis factor-alpha (TNFα) in stroma cells in contact with the melanoma cells in the sample obtained from the subject is higher than a predetermined reference value,
and
ii) administering to the subject a therapeutically effective amount of a TNFα blocking agent.

3. The method of claim 1 , wherein the TNFα blocking agent is etanercept.

4. The method of claim 1 , wherein the TNFα blocking agent is a monoclonal antibody.

5. The method of claim 4 , wherein the monoclonal antibody is infliximab or adalimumab.

6. The method of claim 1 , wherein the TNFα blocking agent is a TNF-R1 antagonist.

7. The method of claim 2 , wherein the TNFα blocking agent is etanercept.

8. The method of claim 2 , wherein the TNFα blocking agent is a monoclonal antibody.

9. The method of claim 8 , wherein the monoclonal antibody is infliximab or adalimumab.

10. The method of claim 2 , wherein the TNFα blocking agent is a TNF-R1 antagonist.

11. A method of treating or inhibiting growth or metastasis of melanoma in a subject in whom melanoma cells express Major Histocompatibility Complex Class I (MHCI) and in whom stroma cells exhibit tumor necrosis factor-alpha (TNFα) expression comprising
administering to the subject a therapeutically effective amount of an anti-TNF-R1 agent when CD8 + tumor infiltrating lymphocytes (TIL) and a high endothelial venule (HEV) MECA79+ differentiation or density are present in a melanoma tumor sample obtained from the subject, and
an expression level of MHCI in melanoma cells in a sample from the subject is higher than a predetermined reference value, and
an expression level of TNFα in stroma cells in a sample from the subject is higher than a predetermined reference value.

12. A method for treating melanoma in a subject comprising the steps of
i) identifying a subject having an infiltration of CD8+ TIL in a melanoma tumor having a high endothelial venule (HEV) MECA79+ differentiation or density within the melanoma tumor,
ii) determining an expression level of Major Histocompatibility Complex Class I (MHCI) in melanoma cells in a sample obtained from the subject and determining an expression level of tumor necrosis factor-alpha (TNFα) in stroma cells in a sample obtained from the subject,
iii) comparing expression levels determined at step ii) with predetermined reference values and
iv) administering to the subject a therapeutically effective amount of an anti-TNF-R1 agent when the expression levels determined at step ii) are higher than the predetermined reference value.

Assignees

• Inst Nat Sante Rech Med
• Ct Hospitalier Universitaire Toulouse
• Inst Claudius Regaud
• Univ Pauls Sabatier Toulouse Iii
• Inst Nat Sante Rech Med
• Univ Toulouse 3 Paul Sabatier

Inventors

• Segui Bruno
• Andrieu-Abadie Nathalie
• Levade Thierry
• Colacios Viatge Celine
• Rochaix Philippe
• Bertrand Florie
• BENOIST Herve
• Rochotte Julia

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• G01N33/5751

  of the skin, e.g. melanoma · CPC title

• A61K38/1793

  for cytokines; for lymphokines; for interferons · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• G01N2333/70539

  MHC-molecules, e.g. HLA-molecules · CPC title