Glycan-interacting compounds and methods of use
The present disclosure provides antibodies with T cell-interacting regions and/or glycan-interacting regions. Bispecific antibodies capable of recruiting T cells to cancer cells are also provided, including bispecific antibodies capable of recruiting T cells to cancer cells expressing sialyl Tn (STn). The present disclosure also includes methods for killing cells by targeting them with antibodies having T cell-interacting regions.
1. A bispecific antibody, comprising a sialyl Tn (STn)-binding region and a CD3-binding region, wherein the STn-binding region comprises a complementarity determining region (CDR)-H1, a CDR-H2, a CDR-H3, a CDR-L1, a CDR-L2, and a CDR-L3 respectively comprising the sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8; or SEQ ID NOs: 9, 10, 11, 12, 7, and 8, and wherein the CD3-binding region comprises a heavy chain variable domain (VH) comprising the sequence of SEQ ID NO: 66 and a light chain variable domain (VL) comprising the sequence of SEQ ID NO: 71.
2. The bispecific antibody of claim 1 , wherein the STn-binding region comprises a heavy chain variable domain (VH) comprising the sequence of SEQ ID NO: 60 and a light chain variable domain (VL) comprising the sequence of SEQ ID NO: 53.
3. The bispecific antibody of claim 1 , wherein the CD3-binding region comprises a single-chain variable fragment (scFv) comprising the sequence of SEQ ID NO: 75 or 77.
4. The bispecific antibody of claim 1 , wherein the antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 91 or 92, and a light chain comprising the sequence of SEQ ID NO: 89.
5. The bispecific antibody of claim 1 , wherein the antibody simultaneously binds a T cell and a cancer cell.
6. The bispecific antibody of claim 1 , wherein the antibody binds the cancer cell with a half maximal effective concentration (EC 50 ) of from about 1 nM to about 50 nM.
7. A composition comprising the bispecific antibody of claim 1 and at least one pharmaceutically acceptable excipient.
8. The bispecific antibody of claim 4 , wherein the antibody simultaneously binds a T cell and a cancer cell.
9. The bispecific antibody of claim 4 , wherein the antibody binds the cancer cell with a half maximal effective concentration (EC 50 ) of from about 1 nM to about 50 nM.
10. A composition comprising the bispecific antibody of claim 4 and at least one pharmaceutically acceptable excipient.