Agents and methods to elicit anti-tumor immune response

Patent metadata

Field	Value
Publication number	US-9334522-B2
Application number	US-44133507-A
Country	US
Kind code	B2
Filing date	Sep 13, 2007
Priority date	Sep 13, 2006
Publication date	May 10, 2016
Grant date	May 10, 2016

Abstract

The invention provides an isolated, purified population of human cells comprising CD8+ T cells with reduced Cbl-b activity. The invention provides uses of such cells in methods for inducing or enhancing an anti-tumor immune response in a subject. These methods comprise: (a) providing a cell population, from a subject or from another source, which comprises CD8+ T cells, (b) reducing Cbl-b activity in the CD8+ T-cells, (c) administering the cells of step (b) to the subject. The invention provides methods for making CD8+ T cells that do not require stimulation through a co-receptor in order for the cell to become activated or proliferated in response to contact via its T cell receptor. Such methods are based upon reducing function of Cbl-b. The invention also provides methods for identifying agents which affect Cbl-b expression or activity.

First claim

What is claimed is:

1. A method for making CD8 + T-cells which do not require co-stimulation in order to become activated and proliferate, the method comprising:
(a) providing CD8 + T-cells, and
(b) reducing Cbl-b activity in the CD8 + T-cells, thereby creating CD8 + T cells which do not require co-stimulation to become activated and proliferate.

2. A method for inducing an anti-tumor immune response in a subject, the method comprising:
(a) providing CD8 + T cells,
(b) reducing Cbl-b activity in the CD8 + T cells, and
(c) administering the cells of step (b) to the subject.

3. The method of claim 1 or 2 , wherein the CD8 + T-cells are provided from peripheral blood, lymph organs, or tumor infiltrates.

4. A method for inducing an anti-tumor immune response in a subject, the method comprising:
(a) isolating from the subject CD8 + T cells,
(b) reducing Cbl-b activity in the CD8 + T cells, and
(c) administering the cells of step (b) to the subject.

5. The method of any one of claim 1 , 2 , or 4 , comprising a step of stimulating the CD8 + T cells to proliferate, wherein the step is performed after step (b).

6. The method of claim 5 , wherein the stimulating of the CD8 + T-cells comprises contacting the CD8 + T cells with an anti-CD3 antibody, incubating the CD8 + T cells with IL-2, or a combination thereof.

7. The method of any one of claim 1 , 2 , or 4 , the method comprising a step of stimulating the CD8 + T cells with tumor cells isolated from the subject, so as to increase the number of tumor specific CD8 + T cells.

8. The method of claim 7 , wherein the method comprises contacting the tumor specific CD8 + T cells with an anti-CD3 antibody or incubating the tumor specific CD8 + T cells with IL-2 or a combination thereof in order to further increase the number of the tumor specific CD8 + T cells.

9. The method of any one of claim 1 , 2 or 4 , wherein reducing Cbl-b activity is achieved by introducing an siRNA which targets Cbl-b in the CD8 + T-cells.

10. The method of any one of claim 2 , or 4 , wherein the subject suffers from any of the following types of tumors: melanoma, lymphoma, or any solid tumors expressing MHC-I with an antigen that can be recognized by cytotoxic T-lymphocytes (CTLs).

11. The method of claim 9 , wherein the siRNA is SEQ ID NO: 1 (5′-CAGGAGTATGAGACAGAAG-3′).

Assignees

• Gu Hua
• Hodes Richard
• Chiang Jeffrey J
• Jang Ihnkyung
• Univ Columbia
• Us Health

Inventors

• Gu Hua
• Hodes Richard
• Chiang Jeffrey J
• Jang Ihnkyung

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P37/04

  Immunostimulants · CPC title

• C12N2310/14

  interfering nucleic acids [NA] · CPC title

• C12N15/113

  Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)} · CPC title

• C12N2501/998

  Proteins not provided for elsewhere · CPC title