Anti-BST2 antibodies targeting BST2 long isoform
Embodiments of the disclosure include methods and compositions directed to targeting of cells that express the long form of Bone marrow stromal cell antigen 2 (BST2) protein, including cancer cells that express the long isoform of BST2. In particular embodiments, monoclonal antibodies or functionally active fragments thereof are utilized to target cells that express the long isoform of BST2. The monoclonal antibodies or functionally active fragments thereof may be utilized by themselves or as part of other entities, such as cells or engineered antigen receptors. The disclosure includes methods of treatment, prevention, and/or diagnosis using the encompassed antibodies or functional fragments thereof.
1 . An antibody or an antigen-binding portion thereof comprising:
(a) three heavy chain CDRs (CDR-H) and three light chain CDRs (CDR-L), wherein: CDR-H1 comprises the amino acid sequence as set forth in SEQ ID NO: 8 (GFNIKDYY), CDR-H2 comprises the amino acid sequence as set forth in SEQ ID NO: 10 (IDPENGDT), CDR-H3 comprises the amino acid sequence as set forth in SEQ ID NO: 12 (KRGD), CDR-L1 comprises the amino acid sequence as set forth in SEQ ID NO: 17 (QSIVHSNGNTY), CDR-L2 comprises the amino acid sequence of KVS, and CDR-L3 comprises the amino acid sequence as set forth in SEQ ID NO: 20 (FQGSHAPFT); and wherein said antibody or antigen-binding portion thereof binds to BST2;
(b) three heavy chain CDRs (CDR-H) and three light chain CDRs (CDR-L), wherein: CDR-H1 comprises the amino acid sequence as set forth in SEQ ID NO: 38 (GYTFTEDT), CDR-H2 comprises the amino acid sequence as set forth in SEQ ID NO: 40 (INPNKGGT), CDR-H3 comprises the amino acid sequence as set forth in SEQ ID NO: 42 (ATLVDY), CDR-L1 comprises the amino acid sequence as set forth in SEQ ID NO: 30 (QNVGTN), CDR-L2 comprises the amino acid sequence of SAS, and CDR-L3 comprises the amino acid sequence as set forth in SEQ ID NO: 33 (QQYNSYPLT); or
(c) three heavy chain CDRs (CDR-H) and three light chain CDRs (CDR-L), wherein: CDR-H1 comprises the amino acid sequence as set forth in SEQ ID NO: 55 (GFSLSTSGVG), CDR-H2 comprises the amino acid sequence as set forth in SEQ ID NO: 57 (IWWDDDE), CDR-H3 comprises the amino acid sequence as set forth in SEQ ID NO: 59 (ARRYYGDAMDY), CDR-L1 comprises the amino acid sequence as set forth in SEQ ID NO: 47 (QSLVHSNGHTY), CDR-L2 comprises the amino acid sequence of KVS, and CDR-L3 comprises the amino acid sequence as set forth in SEQ ID NO: 50 (SQSTHVPYT).
2 . The antibody or an antigen-binding portion thereof of claim 1 , wherein the antibody or an antigen-binding portion thereof comprises a heavy chain variable region that comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO:7 and a light chain variable region that comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 16.
3 . The antibody of claim 1 , wherein the antibody is a monoclonal antibody.
4 . An engineered antigen receptor or a bispecific or a multi-specific antibody comprising the antibody or an antigen-binding portion thereof of claim 1 .
5 . An engineered antigen receptor comprising a scFv, wherein the scFv comprises the antigen-binding portion of claim 1 .
6 . A composition comprising a scFv, wherein the scFv comprises the antigen-binding portion of claim 1 .
7 . An immune cell comprising the engineered antigen receptor of claim 5 .
8 . The cell of claim 7 , wherein the immune cell is a T cell, NK cell, or NKT cell.
9 . A method of detecting BST2-expressing cells in a tissue or plurality of cells that are cancerous or suspected of being cancerous, comprising the step of subjecting the tissue or plurality of cells to an effective amount of the antibody of claim 1 , wherein the antibody binds BST2 in the tissue or plurality of cells.
10 . The method of claim 9 , wherein the tissue or plurality of cells comes from an individual that is known to have cancer or is suspected of having cancer or wherein the tissue or plurality of cells comes from an individual that is known to have metastatic cancer or is suspected of having metastatic cancer.
11 . A method of measuring BST2 in tissue or cells from an individual that has cancer or that is suspected of having cancer, comprising the step of measuring BST2 from the tissue or cells with an effective amount of the antibody of claim 1 .