BISPECIFIC SCFV IMMUNOFUSION (BIF)
Certain embodiments are directed to a bispecific immunoglobulin that is capable of binding cell surface molecules on a target cell, such as cancer cells, and cell surface molecules on immune effector cell, such as cytotoxic T lymphocytes, resulting in the targeted killing of target cells.
1 . A polypeptide comprising a first target binding domain that specifically binds a cancer cell, a second effector binding domain that specifically binds an immunologic effector, and an immunoglobulin constant region linker operatively coupling the first and second binding domain.
2 . The polypeptide of claim 1 , wherein the target binding domain binds a colorectal, lung, breast, kidney, brain, prostate, pancreas, or blood cancer cell or solid malignant tumor cell.
3 . The polypeptide of claim 2 , wherein the target binding domain binds a leukemia cell.
4 . The polypeptide of claim 3 , wherein the target binding domain specifically binds cells expressing CD123, prostate specific membrane antigen (PSMA), TEM8, or CD33.
5 . The polypeptide of claim 4 , wherein the target binding domain specifically binds CD123.
6 . The polypeptide of claim 5 , wherein the target binding domain comprises variable regions that are 95% identical to variable regions of SEQ ID NO:2.
7 . The polypeptide of claim 5 , wherein the target binding domain comprises variable regions having an amino acid sequence of the variable regions of SEQ ID NO:2.
8 . The polypeptide of claim 1 , wherein the target binding domain has the amino sequence of SEQ ID NO:2.
9 . The polypeptide of claim 1 , wherein the immune effector is a lymphocyte.
10 . The polypeptide of claim 9 , wherein the lymphocyte is a CD3+ cytotoxic T lymphocyte.
11 . The polypeptide of claim 1 , wherein the effector binding domain specifically binds CD3.
12 . The polypeptide of claim 11 , wherein the effector binding domain comprises hypervariable regions that are 95% identical to the hypervariable regions of SEQ ID NO:3.
13 . The polypeptide of claim 11 , wherein the effector binding domain comprises hypervariable regions having an amino acid sequence identical to SEQ ID NO:3.
14 . The polypeptide of claim 1 , wherein the immunoglobulin constant region is a human IgG constant region.
15 . The polypeptide of claim 14 , wherein the human IgG constant region is a hinge-C H 2-C H 3 segment of human IgG1.
16 . The polypeptide of claim 14 , wherein the immunoglobulin constant region has an amino acid sequence that is 95% identical to SEQ ID NO:4.
17 . The polypeptide of claim 14 , wherein the immunoglobulin constant region has an amino acid sequence identical to SEQ ID NO:4.
18 . A polypeptide having an amino acid sequence that is 90% identical to SEQ ID NO:1.
19 . A method for treating cancer comprising providing an effective amount of the polypeptide of claim 1 to a cancer patient.