ANTIBODIES HAVING SPECIFICITY FOR BTN2 AND USES THEREOF
The present invention relates to antibodies having specificity for BTN2 and uses thereof, in particular for the treatment of cancer.
1 . A method of inhibiting the response of Vγ9/Vδ2 T cells against BTN2-expressing target cells, comprising contacting Vγ9/Vδ2 T cells with BTN2-expressing target cells and an effective amount of an antibody having specificity for human butyrophilin-2 (BTN2), wherein said antibody inhibits the cytolytic function of activated Vγ9/Vδ2 T cells.
2 . The method of claim 1 , wherein said antibody inhibits the production of IFN-γ and TNF-α of activated Vγ9/Vδ2 T cells and/or inhibits the proliferation of activated Vγ9/Vδ2 T cells.
3 . The method of claim 1 , wherein said antibody competes for binding to BTN2A2 with at least one of the following reference murine antibodies:
i. mAb 4.15 as obtainable by the hybridoma deposited at the CNCM under deposit number CNCM I-5231;
ii. mAb 5.28 as obtainable by the hybridoma deposited at the CNCM under deposit number CNCM I-5232;
iii. mAb 7.28 as obtainable by the hybridoma deposited at the CNCM under deposit number CNCM I-5233;
iv. mAb 7.48 as obtainable by the hybridoma deposited at the CNCM under deposit number CNCM I-5234;
v. mAb 8.15 as obtainable by the hybridoma deposited at the CNCM under deposit number CNCM I-5235; or
vi. mAb 8.16 as obtainable by the hybridoma deposited at the CNCM under deposit number CNCM I-5236.
4 . The method of claim 1 , wherein said antibody does not cross-react with human CD277.
5 . The method of claim 1 , wherein said antibody is a human, chimeric or humanized antibody.
6 . A method of inhibiting an immune or inflammatory response in a subject, comprising administering to the subject an effective amount of an antibody having specificity for human butyrophilin-2 (BTN2), wherein said antibody inhibits the cytolytic function of activated Vγ9/Vδ2 T cells.
7 . The method of claim 6 , wherein said antibody inhibits production of IFN-γ and TNF-α of activated Vγ9/Vδ2 T cells and/or inhibits the proliferation of activated Vγ9/Vδ2 T cells.
8 . The method of claim 6 , wherein said antibody competes for binding to BTN2A2 with at least one of the following reference murine antibodies:
vii. mAb 4.15 as obtainable by the hybridoma deposited at the CNCM under deposit number CNCM I-5231;
viii. mAb 5.28 as obtainable by the hybridoma deposited at the CNCM under deposit number CNCM I-5232;
ix. mAb 7.28 as obtainable by the hybridoma deposited at the CNCM under deposit number CNCM I-5233;
x. mAb 7.48 as obtainable by the hybridoma deposited at the CNCM under deposit number CNCM I-5234;
xi. mAb 8.15 as obtainable by the hybridoma deposited at the CNCM under deposit number CNCM I-5235; or
xii. mAb 8.16 as obtainable by the hybridoma deposited at the CNCM under deposit number CNCM I-5236.
9 . The method of claim 6 , wherein said antibody does not cross-react with human CD277.
10 . The method of claim 6 , wherein said antibody is a human, chimeric or humanized antibody.
11 . A method for obtaining an antibody which inhibits the immune response in a subject, wherein said method comprises:
(a) providing one or more antibodies which selectively bind to human butyrophilin-2 (BTN2);
(b) contacting said one or more antibodies with Vγ9/Vδ2 T cells and BTN2-expressing target cells; and
(c) selecting an antibody which inhibits the cytolytic function of activated Vγ9/Vδ2 T cells.
12 . The method of claim 11 , wherein said selected antibody inhibits production of IFN-γ and TNF-α of activated Vγ9/Vδ2 T cells and/or inhibits the proliferation of activated Vγ9/Vδ2 T cells.
13 . The method of claim 1 , wherein said selected antibody inhibits the degranulation of activated Vγ9/Vδ2 T cells by more than 90%.
14 . The method of claim 11 , wherein step (a) comprises immunizing a mouse expressing human variable region antibodies with BTN2 antigens and obtaining a hybridoma producing an antibody which selectively bind to human butyrophilin-2 (BTN2).
15 . The method of claim 11 , wherein step (a) comprises humanizing an anti-BTN2 antibody.
16 . The method of claim 11 , wherein step (a) comprises screening antibodies for their binding affinity to BTN2.
17 . Wherein the selected antibody competes for binding to BTN2A2 with at least one of the following reference murine antibodies:
xiii. mAb 4.15 as obtainable by the hybridoma deposited at the CNCM under deposit number CNCM I-5231;
xiv. mAb 5.28 as obtainable by the hybridoma deposited at the CNCM under deposit number CNCM I-5232;
xv. mAb 7.28 as obtainable by the hybridoma deposited at the CNCM under deposit number CNCM I-5233;
xvi. mAb 7.48 as obtainable by the hybridoma deposited at the CNCM under deposit number CNCM I-5234;
xvii. mAb 8.15 as obtainable by the hybridoma deposited at the CNCM under deposit number CNCM I-5235; or
xviii. mAb 8.16 as obtainable by the hybridoma deposited at the CNCM under deposit number CNCM I-5236.