Agents for treatment of claudin expressing cancer diseases
The present invention provides binding agents that contain n binding domain that is specific for CD3 allowing binding to T cells and a binding domain that is specific for a tumor-associated claudin molecule and methods of using these binding agents or nucleic acids encoding therefor for treating cancer.
1. A method of treating a cancer disease characterized by cancer cells expressing claudin 6 (CLDN6), the method comprising administering to a patient a pharmaceutical composition, wherein the pharmaceutical composition comprises a binding agent, wherein the binding agent is a bispecific single chain antibody (bi-scFv) comprising a first binding domain and a second binding domain, wherein the first binding domain binds to CD3 and the second binding domain binds to CLDN6, wherein the first binding domain and the second binding domain each comprise a combination of a variable domain of a heavy chain of an immunoglobulin (VH) and a variable domain of a light chain of an immunoglobulin (VL) as defined in SEQ ID NO:45.
2. The method of claim 1 , wherein said second binding domain binds to an extracellular domain of said CLDN6.
3. The method of claim 1 , wherein said first binding domain binds to the epsilon-chain of CD3.
4. The method of claim 1 , wherein said CD3 is expressed on the surface of a T cell.
5. The method of claim 1 , wherein binding of said binding agent to CD3 on T cells results in proliferation and/or activation of said T cells, wherein said activated T cells preferably release cytotoxic factors, e.g. perforins and granzymes, and initiate cytolysis and apoptosis of cancer cells.
6. The method of claim 1 , wherein the bispecific single chain antibody consists of two scFv molecules connected via a linker peptide.
7. The method of claim 1 , wherein said cancer is selected from the group consisting of urinary bladder cancer, ovarian cancer, in particular ovarian adenocarcinoma and ovarian teratocarcinoma, lung cancer, including small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), in particular squamous cell lung carcinoma and adenocarcinoma, gastric cancer, breast cancer, hepatic cancer, pancreatic cancer, skin cancer, in particular basal cell carcinoma and squamous cell carcinoma, malignant melanoma, head and neck cancer, in particular malignant pleomorphic adenoma, sarcoma, in particular synovial sarcoma and carcinosarcoma, bile duct cancer, cancer of the urinary bladder, in particular transitional cell carcinoma and papillary carcinoma, kidney cancer, in particular renal cell carcinoma including clear cell renal cell carcinoma and papillary renal cell carcinoma, colon cancer, small bowel cancer, including cancer of the ileum, in particular small bowel adenocarcinoma and adenocarcinoma of the ileum, testicular embryonal carcinoma, placental choriocarcinoma, cervical cancer, testicular cancer, in particular testicular seminoma, testicular teratoma and embryonic testicular cancer, uterine cancer, germ cell tumors such as a teratocarcinoma or an embryonal carcinoma, in particular germ cell tumors of the testis, and the metastatic forms thereof.
8. The method of claim 1 , wherein the VH comprises an amino acid sequence represented by SEQ ID NO: 22 and the VL comprises an amino acid sequence represented by SEQ ID NO: 23.
9. The method of claim 1 , wherein the binding agent comprises an amino acid sequence according to SEQ ID NO:42.
10. The method of claim 1 , wherein the binding agent comprises an amino acid sequence according to SEQ ID NO:43.
11. The method of claim 1 , wherein the binding agent comprises an amino acid sequence according to SEQ ID NO:44.
12. The method of claim 1 , wherein the binding agent comprises an amino acid sequence according to SEQ ID NO:45.