Bispecific antibody for cancer immunotherapy
View Patent ↗Disclosed are compositions and methods for gene transfer in immune effector cells, e.g. to create chimeric antigen receptors (CARs). In particular, polypeptides are disclosed that comprising an antigen-binding region and a heparin binding domain, wherein the antigen-binding region is capable of specifically binding to an immune cell antigen located on an immune effector cell, and wherein the heparin binding domain is capable of binding a viral vector.
1. A fusion polypeptide comprising an antigen-binding region and a heparin binding domain comprising the amino acid sequence SEQ ID NO:3, wherein the antigen-binding region is capable of specifically binding to an immune cell antigen located on an immune effector cell, and wherein the heparin binding domain is capable of binding a viral vector, and further wherein the immune cell antigen binding region comprises the amino acid sequence SEQ ID NO:1 or SEQ ID NO:2.
2. The polypeptide of claim 1 , wherein the immune effector cell is a member of the human lymphoid lineage.
3. The polypeptide of claim 1 , wherein the immune effector cell is capable of exerting a cytotoxic or an apoptotic effect on a target cell.
4. A fusion polypeptide comprising the following formula:
V L I-V H I--HBD-Fc,
V H I-V L I--HBD-Fc,
HBD--V L I-V H I-Fc,
HBD--V H -V L I-Fc,
Fc-V L I-V H I-HBD,
Fc-V H I-V L I-HBD,
Fc-HBD--V L I-V H I, or
Fc-HBD--V H I-V L I,
wherein “V L I” is a light chain variable domain specific for an immune cell antigen;
wherein “V H I” is a heavy chain variable domain specific for the immune cell antigen;
wherein “HBD” is a heparin binding domain comprising the amino acid sequence SEQ ID NO:3;
wherein “-” consists of a peptide linker or a peptide bond;
wherein “--” consists of a peptide linker or a peptide bond; and
wherein “Fc” consists of an optional Fc domain of an immunoglobulin; and further
wherein V H I and V L I form an immune cell antigen binding region, and wherein the immune cell antigen binding region comprises the amino acid sequence SEQ ID NO:1 or SEQ ID NO:2.
5. A single chain antibody, comprising the polypeptide of claim 4 , wherein the V L I and the V H I have dimerized.
6. An isolated nucleic acid encoding the polypeptide of claim 4 .
7. A vector comprising the isolated nucleic acid of claim 6 operably linked to an expression control sequence.
8. An isolated cell comprising the vector of claim 7 .
9. A method of treating cancer in a human subject comprising administering to the subject a therapeutically effective amount of one or more of the polypeptides of claim 1 .
10. The method of claim 9 , further comprising administering to the subject a checkpoint inhibitor.
11. The method of claim 9 , wherein the checkpoint inhibitor comprises an anti-PD-1 antibody, anti-PD-L1 antibody, anti-CTLA-4 antibody, or a combination thereof.