Disease therapy by inducing immune response to Trop-2 expressing cells
The present invention concerns compositions and methods of use of bispecific antibodies comprising at least one binding site for Trop-2 (EGP-1) and at least one binding site for CD3. The bispecific antibodies are of use for inducing an immune response against a Trop-2 expressing tumor, such as carcinoma of the esophagus, pancreas, lung, stomach, colon, rectum, urinary bladder, breast, ovary, uterus, kidney or prostate. The methods may comprising administering the bispecific antibody alone, or with one or more therapeutic agents such as antibody-drug conjugates, interferons (preferably interferon-α), and/or checkpoint inhibitor antibodies. The bispecific antibody is capable of targeting effector T cells, NK cells, monocytes or neutrophils to induce leukocyte-mediated cytotoxicity of Trop-2 + cancer cells. The cytotoxic immune response is enhanced by co-administration of interferon, checkpoint inhibitor antibody and/or ADC.
1. A method of inducing an immune response to a Trop-2 expressing cancer comprising administering to a subject with a Trop-2 expressing cancer a bispecific antibody that comprises at least one binding site for Trop-2 and at least one binding site for CD3, wherein the bispecific antibody comprises the amino acid sequence of SEQ ID NO:107.
2. The method of claim 1 , wherein the bispecific antibody comprises at least one antibody fragment selected from the group consisting of a scFv, a Fab and a dAb.
3. The method of claim 1 , wherein the Trop-2 expressing cancer is a carcinoma of the esophagus, pancreas, lung, stomach, colon, rectum, urinary bladder, breast, ovary, uterus, kidney or prostate.
4. The method of claim 1 , wherein the bispecific antibody comprises a humanized RS7 (anti-Trop-2) antibody or antigen-binding fragment thereof.
5. The method of claim 1 , wherein the bispecific antibody comprises an Okt3 (anti-CD3) antibody or antigen-binding fragment thereof.
6. The method of claim 1 , wherein the bispecific antibody induces an immune response to a Trop-2 expressing cancer without increasing cytokine production to levels capable of inducing cytokine release syndrome (CRS).
7. The method of claim 1 , wherein the bispecific antibody induces trogocytosis of cell surface antigens between Trop-2 expressing cancer cells and T cells.
8. A bispecific antibody comprising at least one binding site for Trop-2 and at least one binding site for CD3, wherein the bispecific antibody comprises the amino acid sequence of SEQ ID NO:107.
9. The bispecific antibody of claim 8 , wherein the bispecific antibody is capable of inducing an immune response against a Trop-2 expressing cancer when administered to a subject with a Trop-2 expressing cancer.
10. The bispecific antibody of claim 8 , wherein the bispecific antibody comprises a humanized RS7 (anti-Trop-2) antibody or antigen-binding fragment thereof.
11. The bispecific antibody of claim 8 , wherein the bispecific antibody comprises an Okt3 (anti-CD3) antibody or antigen-binding fragment thereof.
12. The bispecific antibody of claim 8 , wherein the bispecific antibody comprises a first and a second antibody fragment selected from the group consisting of an scFv, a Fab and a dAb.
13. The bispecific antibody of claim 9 , wherein the Trop-2 expressing cancer is a carcinoma of the esophagus, pancreas, lung, stomach, colon, rectum, urinary bladder, breast, ovary, uterus, kidney or prostate.
14. The bispecific antibody of claim 8 , wherein the bispecific antibody is capable of inducing an immune response to a Trop-2 expressing cancer without inducing cytokine release syndrome (CRS).
15. The bispecific antibody of claim 8 , wherein the bispecific antibody induces trogocytosis of cell surface antigens between Trop-2 expressing cancer cells and T cells.